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EP-4735475-A2 - SYNTHETIC CYTOKINE RECEPTORS

EP4735475A2EP 4735475 A2EP4735475 A2EP 4735475A2EP-4735475-A2

Abstract

Provided herein are synthetic cytokine receptors, wherein each synthetic cytokine receptor comprises an extracellular domain, a transmembrane domain, and an interleukin 9 receptor (IL-9R) intracellular domain. Also provided herein are engineered cells expressing one or more such synthetic cytokine receptors.

Inventors

  • JOHNSON, LEXUS R.
  • SIURALA, Mikko
  • LIU, RAYMOND
  • CLARK, JOSEPH T.
  • PIRANER, DAN I.

Assignees

  • DISPATCH BIOTHERAPEUTICS, INC.

Dates

Publication Date
20260506
Application Date
20240628

Claims (1)

  1. 30761-20002.40 WHAT IS CLAIMED: 1. A synthetic cytokine receptor that is a homodimer of identical polypeptide chains each comprising an extracellular domain, a transmembrane domain, and an intracellular domain capable of interleukin 9 receptor (IL-9R) signaling. 2. The synthetic cytokine receptor of claim 1, wherein the intracellular domain capable of IL-9R signaling comprises an IL-9R intracellular domain or a variant thereof. 3. The synthetic cytokine receptor of claim 1 or claim 2, wherein the intracellular domain capable of IL-9R signaling comprises a chimeric JAK/STAT fusion domain. 4. A synthetic cytokine receptor, comprising an extracellular domain, a transmembrane domain, and an interleukin 9 receptor (IL-9R) intracellular domain or a variant thereof, wherein the synthetic cytokine receptor is a constitutively active cytokine receptor. 5. The synthetic cytokine receptor of any of claims 1 to 4, wherein the synthetic cytokine receptor is a multimer. 6. The synthetic cytokine receptor of any of claims 2 to 5 that is a multimer of identical polypeptide chains each comprising the extracellular domain, the transmembrane domain and the IL-9R intracellular domain or variant thereof. 7. The synthetic cytokine receptor of claim 5 or claim 6, wherein the multimer is a dimer. 8. The synthetic cytokine receptor of claim 7, wherein the dimer is a homodimer. 9. The synthetic cytokine receptor of any of claims 1 to 8, wherein each polypeptide chain is constitutively multimerized. 10. The synthetic cytokine receptor of any of claims 1 to 9, wherein the synthetic cytokine receptor comprises at least one self-assembly domain. 30761-20002.40 11. The synthetic cytokine receptor of claim 10, wherein the at least one self- assembly domain is the extracellular domain and/or the transmembrane domain. 12. The synthetic cytokine receptor of any of claims 1 to 11, wherein the synthetic cytokine receptor is multimerized through the transmembrane domain and/or the extracellular domain. 13. The synthetic cytokine receptor of any of claims 1 to 12, wherein the synthetic cytokine receptor is multimerized through the transmembrane domain and the extracellular domain. 14. A synthetic cytokine receptor that is a homodimer of identical polypeptide chains each comprising an extracellular domain, a transmembrane domain, and an interleukin 9 receptor (IL-9R) intracellular domain or a variant thereof. 15. The synthetic cytokine receptor of any of claims 1 to 14, wherein the extracellular domain and/or the transmembrane domain are heterologous to the IL-9R. 16. The synthetic cytokine receptor of any of claims 1 to 15, wherein the transmembrane domain and extracellular domain are the transmembrane domain and extracellular domain from the same protein. 17. The synthetic cytokine receptor of any of claims 1 to 15, wherein the transmembrane domain and extracellular domain are the transmembrane domain and extracellular domain from different proteins. 18. The synthetic cytokine receptor of any of claims 1 to 17, wherein the transmembrane domain is 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 amino acids in length. 19. The synthetic cytokine receptor of any of claims 1 to 18, wherein the transmembrane domain comprises a transmembrane domain derived from Glycophorin A 30761-20002.40 (GpA) Carnitine palmitoyltransferase 1 (CPT1), a tumor necrosis factor receptor (TNFR) or Muc24. 20. The synthetic cytokine receptor of any of claims 1 to 18, wherein the transmembrane domain comprises a transmembrane domain derived from Thrombopoietin receptor. 21. The synthetic cytokine receptor of any of claims 1 to 20, wherein the transmembrane domain promotes alpha-helix dimerization. 22. The synthetic cytokine receptor of any of claims 1 to 21, wherein the transmembrane domain comprises the motif GXXXG (SEQ ID NO: 68). 23. The synthetic cytokine receptor of any of claims 1 to 21, wherein the transmembrane domain comprises the motif LIxxGVxxGVxxT (SEQ ID NO: 70). 24. The synthetic cytokine receptor of any of claims 1 to 23, wherein the transmembrane domain is a transmembrane domain derived from Glycophorin A (GpA) or a variant thereof that comprises one or more mutations (e.g, 1, 2, 3, 4, 5 or 6 mutations) compared to a wild-type GpA transmembrane domain, wherein the variant GpA is sufficient to promote alpha-helix dimerization. 25. The synthetic cytokine receptor of any of claims 1 to 24, wherein the transmembrane domain comprises a transmembrane domain derived from Glycophorin A (GpA). 26. The synthetic cytokine receptor of any of claims 1 to 25, wherein the transmembrane domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 22 or SEQ ID NO:43. 27. The synthetic cytokine receptor of any of claims 1 to 26, wherein the transmembrane domain comprises the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 43. 30761-20002.40 28. The synthetic cytokine receptor of any of claims 1 to 22, wherein the transmembrane domain comprises GXXXG (SEQ ID NO: 68) and GXXXA (SEQ ID NO: 69) motifs. 29. The synthetic cytokine receptor of any of claims 1 to 22 and 28, wherein the transmembrane domain comprises a transmembrane domain derived from Carnitine palmitoyltransferase 1 (CPT1). 30. The synthetic cytokine receptor of any of claims 1 to 22, 28 and 29, wherein the transmembrane domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 45. 31. The synthetic cytokine receptor of any of claims 1 to 22 and 28 to 30, wherein the transmembrane domain comprises the amino acid sequence of SEQ ID NO: 45. 32. The synthetic cytokine receptor of any of claims 1 to 21, wherein the synthetic cytokine receptor comprises the motif AXXXA (SEQ ID NO:77) or AXXXS (SEQ ID NO: 78). 33. The synthetic cytokine receptor of any of claims 1 to 22 or 32, wherein the synthetic cytokine receptor comprises the motif ĭPXĭ (SEQ ID NO:75) or ĭTXXAĭ (SEQ ID NO: 76). 34. The synthetic cytokine receptor of any of claims 1 to 22, 32 or 33, wherein the transmembrane domain is derived from a TNFR. 35. The synthetic cytokine receptor of claim 34, wherein the TNFR is TACI, DR5, p75NTR, Fas, TNFR1, TNFR2 or OX40. 36. The synthetic cytokine receptor of any of claims 1 to 22, and 32 to 35, wherein the transmembrane domain comprises a transmembrane domain derived from DR5. 30761-20002.40 37. The synthetic cytokine receptor of any of claims 1 to 22, and 32 to 36, wherein the transmembrane domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 46. 38. The synthetic cytokine receptor of any of claims 1 to 22 and 32 to 37, wherein the transmembrane domain comprises the amino acid sequence of SEQ ID NO: 46. 39. The synthetic cytokine receptor of any of claims 1 to 22, and 32 to 36, wherein the transmembrane domain comprises a transmembrane domain derived from TACI. 40. The synthetic cytokine receptor of any of claims 1 to 22, 32 to 36 and 39, wherein the transmembrane domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 44. 41. The synthetic cytokine receptor of any of claims 1 to 23, 32 to 36, 39 and 40, wherein the transmembrane domain comprises the amino acid sequence of SEQ ID NO: 44. 42. The synthetic cytokine receptor of any of claims 1 to 19, wherein the transmembrane domain comprises 1 to 6 cysteine residues. 43. The synthetic cytokine receptor of any of claims 1 to 19 and 42, wherein the transmembrane domain promotes disulfide-linked dimerization. 44. The synthetic cytokine receptor of claim 43, wherein the disulfide-linked dimerization forms 1 to 4 disulfide bridges between polypeptide chains of the synthetic cytokine receptor. 45. The synthetic cytokine receptor of any of claims 1 to 19 and 42-44, wherein the transmembrane domain is a variant transmembrane domain that comprises one or more mutations compared to a wild-type transmembrane domain to promote homodimerization of the receptor polypeptide. 46. The synthetic cytokine receptor of claim 45, wherein the one or more mutations promote alpha-helix dimerization or disulfide-linked dimerization. 30761-20002.40 47. The synthetic cytokine receptor of claim 45 or claim 46, wherein the one or more mutations introduces at least one cysteine into the transmembrane domain. 48. The synthetic cytokine receptor of any of claims 45 to 47, wherein the one or more mutations introduces a proline into the transmembrane domain. 49. The synthetic cytokine receptor of any of claims 45 to 47, wherein the one or more mutations introduces a threonine into the transmembrane domain. 50. The synthetic cytokine receptor of any of claims 45 to 49, wherein the one or more mutations introduces a trimer peptide of cysteine, proline, and another amino acid other than cysteine or proline into the transmembrane domain. 51. The synthetic cytokine receptor of any of claims 45-50, wherein the one or more mutations introduces a trimer peptide of cysteine, proline, threonine (CPT or TCP) into the transmembrane domain. 52. The synthetic cytokine receptor of any of claims 45-51, wherein the transmembrane domain is a variant IL-7R transmembrane domain and the one or more mutations is in the wild-type transmembrane sequence PILLTISILSFFSVALLVILACVLW (SEQ ID NO: 71). 53. The synthetic cytokine receptor of any of claims 1 to 19 and 42 to 52, wherein the transmembrane domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 6, SEQ ID NO:7 or SEQ ID NO: 21. 54. The synthetic cytokine receptor of any of claims 1 to 19 and 42 to 53, wherein the transmembrane domain comprises the amino acid sequence of SEQ ID NO: 6, SEQ ID NO: 7 or SEQ ID NO:21. 55. The synthetic cytokine receptor of any of claims 1 to 19, wherein the transmembrane domain comprises a transmembrane domain derived from Muc24. 30761-20002.40 56. The synthetic cytokine receptor of any of claims 1 to 19 and 55, wherein the transmembrane domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 23. 57. The synthetic cytokine receptor of any of claims 1 to 19, 55 or 56, wherein the transmembrane domain comprises the amino acid sequence of SEQ ID NO: 23. 58. The synthetic cytokine receptor of any of claims 1 to 57, wherein the extracellular domain is between about 150 to 260 amino acids in length. 59. The synthetic cytokine receptor of any of claims 1 to 58, wherein the extracellular domain is a dimerizing domain. 60. The synthetic cytokine receptor of claim 59, wherein the dimerizing domain comprises a hinge region. 61. The synthetic cytokine receptor of any of claims 1 to 60, wherein the extracellular domain promotes disulfide-linked dimerization. 62. The synthetic cytokine receptor of any of claims 1 to 61, wherein the extracellular domain comprises 1 to 6 cysteine residues. 63. The synthetic cytokine receptor of claim 61 or claim 62, wherein the disulfide- linked dimerization forms 1 to 4 disulfide bridges between polypeptide chains of the synthetic cytokine receptor. 64. The synthetic cytokine receptor of any of claims 1 to 63, wherein the extracellular domain is derived from the extracellular domain of CD34, DAP12, Glycophorin A, CD8, or Muc24. 65. The synthetic cytokine receptor of any of claims 1 to 63, wherein the extracellular domain comprises an extracellular domain derived from Thrombopoietin receptor. 30761-20002.40 66. The synthetic cytokine receptor of any of claims 1 to 65, wherein the extracellular domain comprises an extracellular domain of CD8 or a truncated portion thereof comprising at least one cysteine residue. 67. The synthetic cytokine receptor of any of claims 1 to 66, wherein the extracellular domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 18, SEQ ID NO: 185 or SEQ ID NO: 19. 68. The synthetic cytokine receptor of any of claims 1 to 67, wherein the extracellular domain comprises the amino acid sequence of SEQ ID NO: 18, SEQ ID NO: 185 or SEQ ID NO: 19. 69. The synthetic cytokine receptor of any of claims 1 to 65, wherein the extracellular domain comprises an extracellular domain of CD34 or a truncated portion thereof comprising at least one cysteine residue. 70. The synthetic cytokine receptor of any of claims 1 to 65 and 69, wherein the extracellular domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 4. 71. The synthetic cytokine receptor of any of claims 1 to 65, 69 and 70, wherein the extracellular domain comprises the amino acid sequence of SEQ ID NO: 4. 72. The synthetic cytokine receptor of any of claims 1 to 65, wherein the extracellular domain is an extracellular domain of Muc24 or a truncated portion thereof comprising at least one cysteine residue. 73. The synthetic cytokine receptor of any of claims 1 to 65 and 72, wherein the extracellular domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 20. 74. The synthetic cytokine receptor of any of claims 1 to 65, 72 and 73, wherein the extracellular domain comprises the amino acid sequence of SEQ ID NO: 20. 30761-20002.40 75. The synthetic cytokine receptor of any of claims 1 to 65, wherein the extracellular domain is an extracellular domain of DAP12 or a truncated portion thereof comprising at least one cysteine residue. 76. The synthetic cytokine receptor of any of claims 1 to 65 and 75, wherein the extracellular domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 5. 77. The synthetic cytokine receptor of any of claims 1 to 65, 75 and 76, wherein the extracellular domain comprises the amino acid sequence of SEQ ID NO: 5. 78. The synthetic cytokine receptor of any of claims 1 to 65, wherein the extracellular domain is an extracellular domain of Glycophorin A (GpA) or a truncated portion thereof comprising at least one cysteine residue. 79. The synthetic cytokine receptor of any of claims 1 to 65 and 78, wherein the extracellular domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 16 or SEQ ID NO: 17. 80. The synthetic cytokine receptor of any of claims 1 to 65, 78 and 79, wherein the extracellular domain comprises the amino acid sequence of SEQ ID NO: 16 or SEQ ID NO: 17. 81. The synthetic cytokine receptor of any of claims 2 to 80, wherein the IL-9R intracellular domain or variant thereof is about 100 to 260 amino acids in length. 82. The synthetic cytokine receptor of any of claims 2 to 81, wherein the IL-9R intracellular domain or variant thereof comprises a BOX1 motif and/or a BOX2 motif. 83. The synthetic cytokine receptor of any of claims 2 to 82, wherein the IL-9R intracellular domain or variant thereof comprises a BOX2 motif. 84. The synthetic cytokine receptor of any of claims 2 and 4 to 80, wherein the IL- 9R intracellular domain or variant thereof is 230 amino acids in length. 30761-20002.40 85. The synthetic cytokine receptor of any of claims 1 to 84, wherein the IL-9R intracellular domain or variant thereof is wild-type IL-9R intracellular domain or a variant thereof that comprises one or more mutations compared to the wild-type IL-9R intracellular domain set forth in SEQ ID NO: 8. 86. The synthetic cytokine receptor of claim 85, wherein the one or more mutations comprises one or more amino acid insertions, deletions, and/or substitutions. 87. The synthetic cytokine receptor of claim 85 or claim 86, wherein the one or more mutations promote signaling through STAT1, STAT3, and/or STAT5 pathways. 88. The synthetic cytokine receptor of any of claims 1 to 87, wherein the IL-9R intracellular domain or variant thereof comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 8. 89. The synthetic cytokine receptor of any of claims 1 to 88, wherein the IL-9R intracellular domain or variant thereof comprises an amino acid sequence of SEQ ID NO: 8. 90. The synthetic cytokine receptor of any of claims 1 to 87, wherein the IL-9R intracellular domain or variant thereof comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56. 91. The synthetic cytokine receptor of any of claims 1 to 87 and 90, wherein the IL-9R intracellular domain or variant thereof comprises an amino acid sequence of SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56. 92. The synthetic cytokine receptor of any of claims 1 to 91, wherein the synthetic cytokine receptor comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, 30761-20002.40 SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 65, SEQ ID NO: 66 or SEQ ID NO: 67. 93. The synthetic cytokine receptor of any of claims 1 to 92, wherein the synthetic cytokine receptor comprises an amino acid sequence of SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 65, SEQ ID NO: 66 or SEQ ID NO: 67. 94. The synthetic cytokine receptor of any of claims 2 to 87, wherein the IL-9R intracellular domain or variant thereof comprises one or more amino acid deletions with reference to wild-type IL-9R intracellular domain (SEQ ID NO: 8). 95. The synthetic cytokine receptor of any of claims 2 to 87, wherein the IL-9R intracellular domain or variant thereof is a truncated IL-9R that lacks a contiguous sequence of amino acids at the C-terminus of wild-type IL-9R intracellular domain. 96. The synthetic cytokine receptor of claim 95, wherein the truncated IL-9R intracellular domain or variant thereof is truncated by between 62 and 99 contiguous amino acids from the C-terminus of wild-type IL-9R intracellular domain. 97. The synthetic cytokine receptor of any of claims 2 to 87, wherein the IL-9R intracellular domain or variant thereof is a truncated IL-9R that lacks amino acids 132 to 230 of SEQ ID NO:8 or lacks amino acids 134 to 230 of SEQ ID NO:8. 98. The synthetic cytokine receptor of any of claims 2 to 97, wherein the IL-9R intracellular domain or variant thereof comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 54, SEQ ID NO: 103, or SEQ ID NO: 104. 99. The synthetic cytokine receptor of any of claims 2 to 98, wherein the IL-9R intracellular domain or variant thereof comprises an amino acid sequence of SEQ ID NO: 54, SEQ ID NO: 103, or SEQ ID NO: 104. 30761-20002.40 100. The synthetic cytokine receptor of any of claims 2 to 99, wherein the synthetic cytokine receptor comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, or SEQ ID NO: 63. 101. The synthetic cytokine receptor of any of claims 2 to 100, wherein the synthetic cytokine receptor comprises an amino acid sequence of SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, or SEQ ID NO: 63. 102. The synthetic cytokine receptor of any of claims 2 to 87, wherein the IL-9R intracellular domain or variant thereof comprises one or more amino acid substitutions with reference to wild-type IL-9R intracellular domain (SEQ ID NO: 8). 103. The synthetic cytokine receptor of claim 102, wherein the IL-9R intracellular domain or variant thereof comprises a STAT binding motif or a variant thereof. 104. The synthetic cytokine receptor of claim 103, wherein the STAT binding motif comprises a STAT1, STAT3, and/or STAT5 binding motif. 105. The synthetic cytokine receptor of claim 103 or claim 104, wherein the STAT binding motif comprises YLPQ (SEQ ID NO: 171). 106. The synthetic cytokine receptor of any of claims 103 to 105, wherein the STAT binding motif comprises a variant STAT binding motif. 107. The synthetic cytokine receptor of any of claims 103 to 106, wherein the variant STAT binding motif comprises YRPQ (SEQ ID NO: 172). 108. The synthetic cytokine receptor of any of claims 103 to 106, wherein the variant STAT binding motif comprises YLPL (SEQ ID NO: 173). 109. The synthetic cytokine receptor of any of claims 103 to 106, wherein the variant STAT binding motif comprises YLKQ (SEQ ID NO: 174). 30761-20002.40 110. The synthetic cytokine receptor of any of claims 2 to 109, wherein the variant IL-9R intracellular domain or variant thereof comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 107 or SEQ ID NO: 108, or SEQ ID NO: 109. 111. The synthetic cytokine receptor of any of claims 2 to 110, wherein the variant IL-9R intracellular domain comprises an amino acid sequence of SEQ ID NO: 107 or SEQ ID NO: 108, or SEQ ID NO: 109. 112. The synthetic cytokine receptor of claim 3, wherein the chimeric JAK/STAT fusion domain comprises a JAK binding domain from a type I cytokine receptor and a STAT binding domain from an IL-9R intracellular domain. 113. The synthetic cytokine receptor of claim 112, wherein the IL-9R STAT binding domain comprises amino acid residues 73 to 230 of SEQ ID NO: 8. 114. The synthetic cytokine receptor of claim 112 or claim 113, wherein the STAT binding domain is 59 to 158 amino acids in length and comprises an IL-9R STAT binding motif. 115. The synthetic cytokine receptor of claim 114, wherein the IL-9R STAT binding motif comprises YLPQ (SEQ ID NO: 171). 116. The synthetic cytokine receptor of any of claims 112 to 115, wherein the IL- 9R STAT binding domain is a truncated IL-9R STAT binding domain that lacks a contiguous sequence of amino acids at the N-terminus of SEQ ID NO: 8. 117. The synthetic cytokine receptor of any of claims 112 to 116, wherein the IL- 9R STAT binding domain is a truncated IL-9R STAT binding domain that lacks a contiguous sequence of amino acids at the C-terminus of SEQ ID NO: 8. 118. The synthetic cytokine receptor of any of claims 112 to 117, wherein the IL- 9R STAT binding domain is a truncated IL-9R STAT binding domain that lacks amino acids at positions 1 to 72 and/or 132 to 230 of SEQ ID NO: 8. 30761-20002.40 119. The synthetic cytokine receptor of any of claims 112 to 118, wherein the IL- 9R STAT binding domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 122 or SEQ ID NO: 123. 120. The synthetic cytokine receptor of any of claims 112 to 119, wherein the IL- 9R STAT binding domain comprises an amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 123. 121. The synthetic cytokine receptor of any of claims 112 to 120, wherein the type I cytokine receptor is selected from the group consisting of interleukin 2 receptor (IL-2R), interleukin 4 receptor (IL-4R), interleukin 7 receptor (IL-7R), interleukin 13 receptor (IL- 13R), interleukin 15 receptor (IL-15R), and interleukin 2 receptor (IL-21R). 122. The synthetic cytokine receptor of any of claims 112 to 121, wherein the type I cytokine receptor is IL-7R. 123. The synthetic cytokine receptor of any of claims 112 to 122, wherein the IL- 7R JAK binding domain is 65 amino acids in length and comprises a box 1 motif. 124. The synthetic cytokine receptor of any of claims 112 to 123, wherein the IL- 7R JAK binding domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 121. 125. The synthetic cytokine receptor of claim 112 to 124, wherein the IL-7R JAK binding domain comprises an amino acid sequence of SEQ ID NO: 121. 126. The synthetic cytokine receptor of any of claims 112 to 125, wherein the chimeric JAK/STAT fusion domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 114, SEQ ID NO: 116 or SEQ ID NO: 181. 127. The synthetic cytokine receptor of any of claims 112 to 126, wherein the chimeric JAK/STAT fusion domain comprises an amino acid sequence of SEQ ID NO: 114, SEQ ID NO: 116, or SEQ ID NO: 181. 30761-20002.40 128. The synthetic cytokine receptor of any of claims 1 to 127, wherein the synthetic cytokine receptor comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 113, SEQ ID NO: 115, or SEQ ID NO: 117. 129. The synthetic cytokine receptor of any of claims 1 to 128, wherein the synthetic cytokine receptor comprises an amino acid sequence of SEQ ID NO: 113, SEQ ID NO: 115, or SEQ ID NO: 117. 130. The synthetic cytokine receptor of any of claims 1 to 3 and 14 to 129, wherein the synthetic cytokine receptor is a constitutively active cytokine receptor. 131. The synthetic cytokine receptor of any of claims 1 to 130, wherein the synthetic cytokine receptor elicits signaling through STAT1, STAT3, and/or STAT5 pathways. 132. The synthetic cytokine receptor of claim 131, wherein signaling through STAT1, STAT3, and/or STAT5 is increased compared to STAT1, STAT3, and/or STAT5 signaling via wild-type IL-9R. 133. The synthetic cytokine receptor of claim 131 or claim 132, wherein signaling through STAT1, STAT3, and/or STAT5 is sustained for a longer period of time compared to STAT1, STAT3, and/or STAT5 signaling via wild-type IL-9R. 134. The synthetic cytokine receptor of claim 133, wherein sustained STAT1, STAT3, and/or STAT5 signaling is determined by phosphorylation status of STAT1, STAT3, and/or STAT5. 135. A polynucleotide encoding the synthetic cytokine receptor of any of claims 1 to 134. 136. A vector, comprising the polynucleotide of claim 135, optionally wherein the vector is a viral vector. 30761-20002.40 137. A method of engineering an isolated cell, comprising contacting the cell with the polynucleotide of claim 135 or the vector of claim 136. 138. An engineered cell expressing the synthetic cytokine receptor of any of claims 1 to 137. 139. An engineered cell expressing a synthetic cytokine receptor that is a homodimer of identical polypeptide chains each comprising an extracellular domain, a transmembrane domain, and an intracellular domain capable of interleukin 9 receptor (IL-9R) signaling. 140. The engineered cell of claim 139, wherein the intracellular domain capable of IL-9R signaling comprises an IL-9R intracellular domain or a variant thereof. 141. The engineered cell of claim 139 or claim 140, wherein the intracellular domain capable of IL-9R signaling comprises a chimeric JAK/STAT fusion domain. 142. An engineered cell expressing a synthetic cytokine receptor, wherein the synthetic cytokine receptor comprises an extracellular domain, a transmembrane domain, and an interleukin 9 receptor (IL-9R) intracellular domain or a variant thereof, wherein the synthetic cytokine receptor is a constitutively active cytokine receptor. 143. The engineered cell of any of claims 139 to 142, wherein the synthetic cytokine receptor is a multimer. 144. The engineered cell of any of claims 139 to 142, wherein the synthetic cytokine receptor is a multimer of identical polypeptide chains each comprising the extracellular domain, the transmembrane domain and the IL-9R intracellular domain or a variant thereof. 145. The engineered cell of claim 143 or claim 144 , wherein the multimer is a dimer. 146. The engineered cell of claim 145, wherein the dimer is a homodimer. 30761-20002.40 147. The engineered cell of any of claims 138 to 146, wherein each polypeptide chain is constitutively multimerized 148. The engineered cell of any of claims 139 to 147, wherein the synthetic cytokine receptor comprises at least one self-assembly domain. 149. The engineered cell of claim 148, wherein the at least one self-assembly domain is the extracellular domain and/or the transmembrane domain. 150. The engineered cell of any of claims 139 to 149, wherein the synthetic cytokine receptor is multimerized through the transmembrane domain and/or the extracellular domain. 151. The engineered cell of any of claims 139 to 150, wherein the synthetic cytokine receptor is multimerized through the transmembrane domain and the extracellular domain. 152. An engineered cell expressing a synthetic cytokine receptor that is a homodimer of identical polypeptide chains each comprising an extracellular domain, a transmembrane domain, and an interleukin 9 receptor (IL-9R) intracellular domain or a variant thereof. 153. The engineered cell of any of claims 139 to 152, wherein the extracellular domain and/or the transmembrane domain are heterologous to the IL-9R. 154. The engineered cell of any of claims 139 to 153, wherein the transmembrane domain and extracellular domain are the transmembrane domain and extracellular domain from the same protein. 155. The engineered cell of any of claims 139 to 153, wherein the transmembrane domain and extracellular domain are the transmembrane domain and extracellular domain from different proteins. 30761-20002.40 156. The engineered cell of any of claims139 to 155, wherein the transmembrane domain is 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 amino acids in length. 157. The engineered cell of any of claims 139 to 156, wherein the transmembrane domain comprises a transmembrane domain derived from Glycophorin A (GpA) Carnitine palmitoyltransferase 1 (CPT1), a tumor necrosis factor receptor (TNFR) or Muc24. 158. The engineered cell of any of claims 139 to 156, wherein the transmembrane domain comprises a transmembrane domain derived from Thrombopoietin receptor. 159. The engineered cell of any of claims 139 to 158, wherein the transmembrane domain promotes alpha-helix dimerization. 160. The engineered cell of any of claims 139 to 159, wherein the transmembrane domain comprises the motif GXXXG (SEQ ID NO: 68). 161. The engineered cell of any of claims 139 to 159, wherein the transmembrane domain comprises the motif LixxGVxxGVxxT (SEQ ID NO: 70). 162. The engineered cell of any of claims 139 to 161, wherein the transmembrane domain is a transmembrane domain derived from Glycophorin A (GpA) or a variant thereof that comprises one or more mutations (e.g, 1, 2, 3, 4, 5 or 6 mutations) compared to a wild- type GpA transmembrane domain, wherein the variant GpA is sufficient to promote alpha- helix dimerization. 163. The engineered cell of any of claims 139 to 162, wherein the transmembrane domain comprises a transmembrane domain derived from Glycophorin A (GpA). 164. The engineered cell of any of claims 139 to 163, wherein the transmembrane domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 22 or SEQ ID NO:43. 165. The engineered cell of any of claims 139 to 164, wherein the transmembrane domain comprises the amino acid sequence of SEQ ID NO: 22 or SEQ ID NO: 43. 30761-20002.40 166. The engineered cell of any of claims 139 to 160, wherein the transmembrane domain comprises GXXXG (SEQ ID NO: 68) and GXXXA (SEQ ID NO: 69) motifs. 167. The engineered cell of any of claims 139 to 160 and 166, wherein the transmembrane domain comprises a transmembrane domain derived from Carnitine palmitoyltransferase 1 (CPT1). 168. The engineered cell of any of claims 139 to 160, 166 and 167, wherein the transmembrane domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 45. 169. The engineered cell of any of claims 139 to 160 and 166 to 168, wherein the transmembrane domain comprises the amino acid sequence of SEQ ID NO: 45. 170. The engineered cell of any of claims 139 to 169, wherein the synthetic cytokine receptor comprises the motif AXXXA (SEQ ID NO:77) or AXXXS (SEQ ID NO: 78). 171. The engineered cell of any of claims 139 to 160 or 170, wherein the synthetic cytokine receptor comprises the motif ĭPXĭ (SEQ ID NO:75) or ĭTXXAĭ (SEQ ID NO: 76). 172. The engineered cell of any of claims 139 to 160, 170 or 171, wherein the transmembrane domain is derived from a TNFR. 173. The engineered cell of claim 172, wherein the TNFR is TACI, DR5, p75NTR, Fas, TNFR1, TNFR2 or OX40. 174. The engineered cell of any of claims 139 to 160, and 170 to 173, wherein the transmembrane domain comprises a transmembrane domain derived from DR5. 30761-20002.40 175. The engineered cell of any of claims 139 to 160 and 170 to 174, wherein the transmembrane domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 46. 176. The engineered cell of any of claims 139 to 160 and 170 to 175, wherein the transmembrane domain comprises the amino acid sequence of SEQ ID NO: 46. 177. The engineered cell of any of claims 139 to 160 and 170 to 174, wherein the transmembrane domain comprises a transmembrane domain derived from TACI. 178. The engineered cell of any of claims 139 to 160, 170 to 174 and 177, wherein the transmembrane domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 44. 179. The engineered cell of any of claims 39 to 161, 170 to 174, 177 and 178, wherein the transmembrane domain comprises the amino acid sequence of SEQ ID NO: 44. 180. The engineered cell of any of claims 139 to 158, wherein the transmembrane domain comprises 1 to 6 cysteine residues. 181. The engineered cell of any of claims 139 to 158 and 180, wherein the transmembrane domain promotes disulfide-linked dimerization. 182. The engineered cell of claim 181, wherein the disulfide-linked dimerization forms 1 to 4 disulfide bridges between polypeptide chains of the synthetic cytokine receptor. 183. The engineered cell of any of claims 139 to 158 and 180 to 182, wherein the transmembrane domain is a variant transmembrane domain that comprises one or more mutations compared to a wild-type transmembrane domain to promote homodimerization of the receptor polypeptide. 184. The engineered cell of claim 183, wherein the one or more mutations promote alpha-helix dimerization or disulfide-linked dimerization. 30761-20002.40 185. The engineered cell of claim 183 or claim 184, wherein the one or more mutations introduces at least one cysteine into the transmembrane domain. 186. The engineered cell of any of claims 183 to 185, wherein the one or more mutations introduces a proline into the transmembrane domain. 187. The engineered cell of any of claims 183 to 185, wherein the one or more mutations introduces a threonine into the transmembrane domain. 188. The engineered cell of any of claims 183 to 187, wherein the one or more mutations introduces a trimer peptide of cysteine, proline, and another amino acid other than cysteine or proline into the transmembrane domain. 189. The engineered cell of any of claims 183 to 188, wherein the one or more mutations introduces a trimer peptide of cysteine, proline, threonine (CPT or TCP) into the transmembrane domain. 190. The engineered cell of any of claims 183 to 188, wherein the transmembrane domain is a variant IL-7R transmembrane domain and the one or more mutations is in the wild-type transmembrane sequence PILLTISILSFFSVALLVILACVLW (SEQ ID NO: 71). 191. The engineered cell of any of claims 139 to 158 and 180 to 190, wherein the transmembrane domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 6, SEQ ID NO:7 or SEQ ID NO: 21. 192. The engineered cell of any of claims 139 to 158 and 180 to 191, wherein the transmembrane domain comprises the amino acid sequence of SEQ ID NO: 6, SEQ ID NO: 7 or SEQ ID NO:21. 193. The engineered cell of any of claims 139 to 158, wherein the transmembrane domain comprises a transmembrane domain derived from Muc24. 30761-20002.40 194. The engineered cell of any of claims 139 to 158 and 193, wherein the transmembrane domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 23. 195. The engineered cell of any of claims 139 to 158, 193 or 194, wherein the transmembrane domain comprises the amino acid sequence of SEQ ID NO: 23. 196. The engineered cell of any of claims 139 to 195, wherein the extracellular domain is between about 150 to 260 amino acids in length. 197. The engineered cell of any of claims 139 to 196, wherein the extracellular domain is a dimerizing domain. 198. The engineered cell of claim 197, wherein the dimerizing domain comprises a hinge region. 199. The engineered cell of any of claims 139 to 198, wherein the extracellular domain promotes disulfide-linked dimerization. 200. The engineered cell of any of claims 139 to 199, wherein the extracellular domain comprises 1 to 6 cysteine residues. 201. The engineered cell of claim 199 or claim 200, wherein the disulfide-linked dimerization forms 1 to 4 disulfide bridges between polypeptide chains of the synthetic cytokine receptor. 202. The engineered cell of any of claims 139 to 201, wherein the extracellular domain is derived from the extracellular domain of CD34, DAP12, Glycophorin A, CD8, or Muc24. 203. The engineered cell of any of claims 139 to 202, wherein the extracellular domain comprises an extracellular domain derived from Thrombopoietin receptor. 30761-20002.40 204. The engineered cell of any of claims 139 to 203, wherein the extracellular domain comprises an extracellular domain of CD8 or a truncated portion thereof comprising at least one cysteine residue. 205. The engineered cell of any of claims 139 to 204, wherein the extracellular domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 18 or SEQ ID NO: 19. 206. The engineered cell of any of claims 139 to 205, wherein the extracellular domain comprises the amino acid sequence of SEQ ID NO: 18 or SEQ ID NO: 19. 207. The engineered cell of any of claims 139 to 203, wherein the extracellular domain comprises an extracellular domain of CD34 or a truncated portion thereof comprising at least one cysteine residue. 208. The engineered cell of any of claims 139 to 203 and 207, wherein the extracellular domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 4. 209. The engineered cell of any of claims 139 to 203, 207 and 208, wherein the extracellular domain comprises the amino acid sequence of SEQ ID NO: 4. 210. The engineered cell of any of claims 139 to 203, wherein the extracellular domain is an extracellular domain of Muc24 or a truncated portion thereof comprising at least one cysteine residue. 211. The engineered cell of any of claims 139 to 203 and 210, wherein the extracellular domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 20. 212. The engineered cell of any of claims 139 to 203, 210 and 211, wherein the extracellular domain comprises the amino acid sequence of SEQ ID NO: 20. 30761-20002.40 213. The synthetic cytokine receptor of any of claims 139 to 203, wherein the extracellular domain is an extracellular domain of DAP12 or a truncated portion thereof comprising at least one cysteine residue. 214. The engineered cell of any of claims 139 to 203 and 213, wherein the extracellular domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 5. 215. The engineered cell of any of claims 139 to 203, 213 and 214, wherein the extracellular domain comprises the amino acid sequence of SEQ ID NO: 5. 216. The synthetic cytokine receptor of any of claims 139 to 203, wherein the extracellular domain is an extracellular domain of Glycophorin A (GpA) or a truncated portion thereof comprising at least one cysteine residue. 217. The engineered cell of any of claims 139 to 203 and 216, wherein the extracellular domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 16 or SEQ ID NO: 17. 218. The engineered cell of any of claims 139 to 203, 216 and 217, wherein the extracellular domain comprises the amino acid sequence of SEQ ID NO: 16 or SEQ ID NO: 17. 219. The engineered cell of any of claims 139 to 218, wherein the IL-9R intracellular domain or variant thereof is about 100 to 260 amino acids in length. 220. The engineered cell of any of claims 139 to 219, wherein the IL-9R intracellular domain or variant thereof comprises a BOX1 motif and/or a BOX2 motif. 221. The engineered cell of any of claims 139 to 220, wherein the IL-9R intracellular domain or variant thereof comprises a BOX2 motif. 222. The engineered cell of any of claims 2 and 4 to 80, wherein the IL-9R intracellular domain or variant thereof is 230 amino acids in length. 30761-20002.40 223. The engineered cell of any of claims 139 to 222, wherein the IL-9R intracellular domain or variant thereof is wild-type IL-9R intracellular domain or a variant thereof that comprises one or more mutations compared to the wild-type IL-9R intracellular domain set forth in SEQ ID NO: 8. 224. The engineered cell of any of claims 139 to 223, wherein the one or more mutations comprises one or more amino acid insertions, deletions, and/or substitutions. 225. The engineered cell of claim 223 or claim 224, wherein the one or more mutations promote signaling through STAT1, STAT3, and/or STAT5 pathways. 226. The engineered cell of any of claims 139 to 225, wherein the IL-9R intracellular domain or variant thereof comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 8. 227. The engineered cell of any of claims 139 to 226, wherein the IL-9R intracellular domain or variant thereof comprises an amino acid sequence of SEQ ID NO: 8. 228. The engineered cell of any of claims 139 to 225, wherein the IL-9R intracellular domain or variant thereof comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56. 229. The engineered cell of any of claims 139 to 225 and 228, wherein the IL-9R intracellular domain or variant thereof comprises an amino acid sequence of SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, or SEQ ID NO: 56. 230. The engineered cell of any of claims 139 to 229, wherein the synthetic cytokine receptor comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, 30761-20002.40 SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 65, SEQ ID NO: 66 or SEQ ID NO: 67. 231. The engineered cell of any of claims 139 to 230, wherein the synthetic cytokine receptor comprises an amino acid sequence of SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 65, SEQ ID NO: 66 or SEQ ID NO: 67. 232. The engineered cell of any of claims 140 to 231, wherein the IL-9R intracellular domain or variant thereof comprises one or more amino acid deletions with reference to wild-type IL-9R intracellular domain (SEQ ID NO: 8). 233. The engineered cell of any of claims 140 to 232, wherein the IL-9R intracellular domain or variant thereof is a truncated IL-9R that lacks a contiguous sequence of amino acids at the C-terminus of wild-type IL-9R intracellular domain. 234. The engineered cell of claim 233, wherein the truncated IL-9R intracellular domain or variant thereof is truncated by between 62 and 99 contiguous amino acids from the C-terminus of wild-type IL-9R intracellular domain. 235. The engineered cell of any of claims 140 to 232, wherein the IL-9R intracellular domain or variant thereof is a truncated IL-9R that lacks amino acids 132 to 230 of SEQ ID NO:8 or lacks amino acids 134 to 230 of SEQ ID NO:8. 236. The engineered cell of any of claims 140 to 235, wherein the IL-9R intracellular domain or variant thereof comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 54, SEQ ID NO: 103, or SEQ ID NO: 104. 237. The engineered cell of any of claims 140 to 236, wherein the IL-9R intracellular domain or variant thereof comprises an amino acid sequence of SEQ ID NO: 54, SEQ ID NO: 103, or SEQ ID NO: 104. 30761-20002.40 238. The engineered cell of any of claims 140 to 237, wherein the synthetic cytokine receptor comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, or SEQ ID NO: 63. 239. The engineered cell of any of claims 140 to 238, wherein the synthetic cytokine receptor comprises an amino acid sequence of SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, or SEQ ID NO: 63. 240. The engineered cell of any of claims 140 to 225, wherein the IL-9R intracellular domain or variant thereof comprises one or more amino acid substitutions with reference to wild-type IL-9R intracellular domain (SEQ ID NO: 8). 241. The engineered cell of claim 240, wherein the IL-9R intracellular domain or variant thereof comprises a STAT binding motif or a variant thereof. 242. The engineered cell of claim 241, wherein the STAT binding motif comprises a STAT1, STAT3, and/or STAT5 binding motif. 243. The engineered cell of claim 241 or claim 242, wherein the STAT binding motif comprises YLPQ (SEQ ID NO: 171). 244. The engineered cell of any of claims 241 to 243, wherein the STAT binding motif comprises a variant STAT binding motif. 245. The engineered cell of any of claims 241 to 244, wherein the variant STAT binding motif comprises YRPQ (SEQ ID NO: 172). 246. The engineered cell of any of claims 241 to 244, wherein the variant STAT binding motif comprises YLPL (SEQ ID NO: 173). 247. The engineered cell of any of claims 241 to 244, wherein the variant STAT binding motif comprises YLKQ (SEQ ID NO: 174). 30761-20002.40 248. The engineered cell of any of claims 140 to 247, wherein the variant IL-9R intracellular domain or variant thereof comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 107 or SEQ ID NO: 108, or SEQ ID NO: 109. 249. The engineered cell of any of claims 140 to 248, wherein the variant IL-9R intracellular domain comprises an amino acid sequence of SEQ ID NO: 107 or SEQ ID NO: 108, or SEQ ID NO: 109. 250. The engineered cell of claim 141, wherein the chimeric JAK/STAT fusion domain comprises a JAK binding domain from a type I cytokine receptor and a STAT binding domain from an IL-9R intracellular domain. 251. The engineered cell of claim 250, wherein the IL-9R STAT binding domain comprises amino acid residues 73 to 230 of SEQ ID NO: 8. 252. The engineered cell of claim 250 or claim 251, wherein the STAT binding domain is 59 to 158 amino acids in length and comprises an IL-9R STAT binding motif. 253. The engineered cell of claim 252, wherein the IL-9R STAT binding motif comprises YLPQ (SEQ ID NO: 171). 254. The engineered cell of any of claims 250 to 253, wherein the IL-9R STAT binding domain is a truncated IL-9R STAT binding domain that lacks a contiguous sequence of amino acids at the N-terminus of SEQ ID NO: 8. 255. The engineered cell of any of claims 250 to 254, wherein the IL-9R STAT binding domain is a truncated IL-9R STAT binding domain that lacks a contiguous sequence of amino acids at the C-terminus of SEQ ID NO: 8. 256. The engineered cell of any of claims 250 to 255, wherein the IL-9R STAT binding domain is a truncated IL-9R STAT binding domain that lacks amino acids at positions 1 to 72 and/or 132 to 230 of SEQ ID NO: 8. 30761-20002.40 257. The engineered cell of any of claims 250 to 256, wherein the IL-9R STAT binding domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 122 or SEQ ID NO: 123. 258. The engineered cell of any of claims 250 to 257, wherein the IL-9R STAT binding domain comprises an amino acid sequence of SEQ ID NO: 122 or SEQ ID NO: 123. 259. The engineered cell of any of claims 250 to 258, wherein the type I cytokine receptor is selected from the group consisting of interleukin 2 receptor (IL-2R), interleukin 4 receptor (IL-4R), interleukin 7 receptor (IL-7R), interleukin 13 receptor (IL-13R), interleukin 15 receptor (IL-15R), and interleukin 2 receptor (IL-21R). 260. The engineered cell of any of claims 250 to 259, wherein the type I cytokine receptor is IL-7R. 261. The engineered cell of any of claims 250 to 260, wherein the IL-7R JAK binding domain is 65 amino acids in length and comprises a box 1 motif. 262. The engineered cell of any of claims 250 to 261, wherein the IL-7R JAK binding domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 121. 263. The engineered cell of claim 250 to 262, wherein the IL-7R JAK binding domain comprises an amino acid sequence of SEQ ID NO: 121. 264. The engineered cell of any of claims 250 to 263, wherein the chimeric JAK/STAT fusion domain comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 114, SEQ ID NO: 116 or SEQ ID NO: 181. 265 The engineered cell of any of claims 250 to 264, wherein the chimeric JAK/STAT fusion domain comprises an amino acid sequence of SEQ ID NO: 114, SEQ ID NO: 116 or SEQ ID NO: 181. 30761-20002.40 266. The engineered cell of any of claims 139 to 265, wherein the synthetic cytokine receptor comprises an amino acid sequence that is at least about 85% identical to SEQ ID NO: 113, SEQ ID NO: 115, or SEQ ID NO: 117. 267. The engineered cell of any of claims 139 to 266, wherein the synthetic cytokine receptor comprises an amino acid sequence of SEQ ID NO: 113, SEQ ID NO: 115, or SEQ ID NO: 117. 268. The engineered cell of any of claims 139 to 141 and 152 to 267, wherein the synthetic cytokine receptor is a constitutively active cytokine receptor. 269. The engineered cell of any of claims 139 to 268, wherein the synthetic cytokine receptor elicits signaling through STAT1, STAT3, and/or STAT5 pathways. 270. The engineered cell of claim 269, wherein signaling through STAT1, STAT3, and/or STAT5 is increased compared to STAT1, STAT3, and/or STAT5 signaling via wild- type IL-9R. 271. The engineered cell of claim 269 or claim 270, wherein signaling through STAT1, STAT3, and/or STAT5 is sustained for a longer period of time compared to STAT1, STAT3, and/or STAT5 signaling via wild-type IL-9R. 272. The engineered cell of claim 271, wherein sustained STAT1, STAT3, and/or STAT5 signaling is determined by phosphorylation status of STAT1, STAT3, and/or STAT5. 273. The engineered cell of any of claims 139 to 272, wherein the engineered cell further expresses at least one different type of engineered receptor. 274. The engineered cell of claim 273, wherein the at least one different type of engineered receptor is a chimeric antigen receptor. 275. The engineered cell of claim 274, wherein the extracellular domain of the chimeric antigen receptor binds to an antigen expressed on a cancer cell. 30761-20002.40 276. The engineered cell of claim 275, wherein the extracellular domain of the chimeric antigen receptor binds to an idiotype of an antibody. 277. The engineered cell of claim 276, wherein the antibody is against an antigen expressed on a cancer cell. 278 The engineered cell of claim 277, wherein the cancer cell is a blood cancer cell or a solid tumor cancer cell. 279. The engineered cell of any of claims 139 to 278, wherein the cell is an immune cell. 280. The engineered cell of any of claims 139 to 279, wherein the cell is a lymphocyte. 281. The engineered cell of any of claims 139 to 280, wherein the engineered cell is an immune effector cell. 282. The engineered cell of any of claims 139 to 281, wherein the cell is a T cell or a Natural Killer (NK) cell. 283. The engineered cell of claim 139 to 282, wherein the cell is a T cell and the T cell is a CD4+ T cell or a CD8+ T cell. 284. The engineered cell of claim 283, wherein the immune effector cell is a cytotoxic T cell. 285. The engineered cell of claim 283, wherein the immune effector cell is a natural killer cell. 286. The engineered cell of any of claims 139 to 285, wherein the cell is a primary cell. 30761-20002.40 287. The engineered cell of any of claims 139 to 286, wherein the cell is a human cell. 288. A population of cells, comprising at least one engineered cell of any of claims 139 to 287. 289. The population of cells of claim 288, wherein the at least one engineered cell comprises engineered CD4+ T cells and engineered CD8+ T cells. 290. A pharmaceutical composition comprising the engineered cell of any of claims 90 to 191 or the population of cells of claim 288 or claim 289. 291. The pharmaceutical composition of claim 290, wherein the pharmaceutical composition further comprises a pharmaceutical acceptable carrier. 292. The pharmaceutical composition of claim 290 or claim 291, wherein the pharmaceutical composition further comprises a cryoprotectant 293. The pharmaceutical composition of any of claims 290 to 292, for use in treating a cancer in a subject. 294. A method of treating a disease or condition in a subject, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of any of claims 290 to 293. 295. The method of claims 294, wherein the disease or condition is a cancer. 296. The method of claim 294 or claim 295, wherein the engineered cell of the pharmaceutical composition expresses an engineered antigen receptor that binds to an antigen expressed on a cell of the cancer. 297. The method of claim 296, wherein the engineered antigen receptor is a chimeric antigen receptor. 30761-20002.40 298. The method of claim 296, wherein the engineered antigen receptor is a T cell receptor. 299. A method of improving function of an immune cell, comprising introducing to the immune cell the polynucleotide of claim 135 or the vector of claim 136, wherein improving immune cell function comprises increased STAT1, STAT3, and/or STAT5 signaling compared to an immune cell expressing wild-type IL-9R. 300. A method of improving cytotoxicity of an immune cell, comprising introducing to the immune cell the polynucleotide of claim 135 or the vector of claim 136, wherein improving immune cell cytotoxicity comprises increased target cell killing compared to an immune cell expressing wild-type IL-9R. 301. A method of improving viability of an immune cell, comprising introducing to the immune cell the polynucleotide of claim 135 or the vector of claim 136, wherein improving viability of the immune cell comprises decreased immune cell death compared to an immune cell expressing wild-type IL-9R. 302. A method of improving cytokine secretion by an immune cell, comprising introducing to the immune cell the polynucleotide of claim 135 or the vector of claim 136, wherein improving cytokine secretion comprises increased secretion of interferon compared to an immune cell expressing wild-type IL-9R. 303. The method of claim 302, wherein the interferon comprises IFNȖ. 304. The method of any of claims 299 to 303, wherein the immune cell further comprises an engineered antigen receptor. 305. The method of claim 304, wherein the one different type of engineered receptor is a chimeric antigen receptor (CAR). 306. The method of claim 305, wherein the extracellular domain of the CAR binds to an antigen expressed on a cancer cell. 30761-20002.40 307. The method of claim 306, wherein the cancer cell is a blood cancer cell or a solid tumor cancer cell. 308. The method of any of claims 299 to 307, wherein the immune cell is a lymphocyte. 309. The method of any of claims 299 to 308, wherein the immune cell is an effector cell. 310. The method of any of claims 299 to 309, wherein the immune cell is a T cell or NK cell. 311. The method of any of claims 299 to 303, wherein the immune cell is a T cell. 312. The method of any of claims 299 to 310, wherein the immune cell is a T cell and the T cell is a CD4+ T cell or a CD8+ T cell. 313. The method of any of claims 299 to 310, wherein the immune cell is a cytotoxic T cell. 314. The method of any of claims 299 to 311, wherein the immune cell is a NK cell. 315. The method of any of claims 299 to 313, wherein the immune cell is a primary cell. 316. A method of improving function of an immune cell, comprising introducing to the immune cell the polynucleotide of claim 135 or the vector of claim 136, thereby improving function of the immune cell. 317. The method of claim 316, wherein improving immune cell function comprises one or more of increased STAT signaling, increased cytotoxicity, increased proliferation, increased viability, increased cytokine secretion, and increased cytotoxic protein secretion compared to a reference cell. 30761-20002.40 318. The method of claim 317, wherein the reference cell comprises a non- engineered immune cell or an engineered immune cell. 319. The method of claim 318, wherein the engineered immune cell expresses a engineered antigen receptor. 320. The method of claim 319, wherein the engineered antigen receptor is a wild- type IL-9R, a chimeric antigen receptor (CAR) or a T cell receptor (TCR). 321. The method of any of claims 317-320, wherein increased STAT signaling comprises increased STAT1, STAT3 and/or STAT5 signaling. 322. The method of any of claims 317-321, wherein increased cytotoxicity comprises increased killing of a target cell. 323. The method of any of claims 317-322, wherein increased cytokine secretion comprises increased secretion of one or more of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-10 (IL-10), and TNFĮ. 324. The method of any of claims 317-323, wherein increased cytotoxic protein secretion comprises increased secretion of one or more of granzyme A, granzyme B, granulysin and perforin. 325. The method of any of claims 317-324, wherein increased viability comprises decreased cell death. 326. The method of any of claims 316-325, wherein the immune cell is a lymphocyte. 327. The method of any of claims 316-326, wherein the immune cell is an effector cell. 30761-20002.40 328. The method of any of claims 316-327, wherein the immune cell is a T cell or NK cell. 329. The method of any of claims 316-327, wherein the immune cell is a T cell and the T cell is a CD4+ T cell or a CD8+ T cell. 330. The method of any of claims 316-329, wherein the immune cell is a cytotoxic T cell. 331. The method of any of claims 316-328, wherein the immune cell is a NK cell. 332. The method of any of claims 316-331, wherein the immune cell is a primary cell.

Description

30761-20002.40 SYNTHETIC CYTOKINE RECEPTORS CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority to U.S. Provisional Patent Application No.63/510,921 filed on June 29, 2023, entitled “SYNTHETIC CYTOKINE RECEPTORS”, U.S. Provisional Patent Application No.63/615,248 filed on December 27, 2023, entitled “SYNTHETIC CYTOKINE RECEPTORS”, and U.S. Provisional Patent Application No.63/555,875 filed on February 20, 2024, entitled “SYNTHETIC CYTOKINE RECEPTORS”, the contents of which are incorporated by reference in their entirety. REFERENCE TO AN ELECTRONIC SEQUENCE LISTING [0002] The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled 30761-2000240.XML created June 28, 2024, which is 277,183 bytes in size. The information in the electronic format of the Sequence Listing is incorporated by reference in its entirety. FIELD [0003] The present disclosure generally relates to synthetic cytokine receptors and engineered cells expressing one or more such synthetic cytokine receptors. BACKGROUND [0004] Therapies that use adoptively transferred genetically engineered T cells have shown substantial anti-tumor activity in patients with hematopoietic malignancies. However, such therapies have limited benefit in patients with solid tumors. One major limitation is the poor in vivo expansion and persistence of adoptively transferred T cells. To circumvent this limitation, patients have been lymphodepleted with chemotherapy and/or radiation prior to being transferred with engineered T cells. However, some patients are too weak to receive toxic regimens such as chemotherapy and radiation. The other major limitation is that the T cells that do successfully expand and persist in vivo become terminally differentiated and dysfunctional. Thus, improved systems and engineered cells are needed to address these problems. Provided embodiments address these needs. SUMMARY [0005] The present disclosure provides synthetic cytokine receptors, engineered cells expressing one or more such synthetic cytokine receptors, and uses thereof. 30761-20002.40 [0006] In some embodiments, provided herein is a synthetic cytokine receptor, comprising an extracellular domain, a transmembrane domain, and an interleukin 9 receptor (IL-9R) intracellular domain. [0007] In some embodiments, provided herein is a polynucleotide encoding a synthetic cytokine receptor, wherein the synthetic cytokine receptor comprises an extracellular domain, a transmembrane domain, and an interleukin 9 receptor (IL-9R) intracellular domain. [0008] In some embodiments, provided herein is a vector comprising a polynucleotide encoding a synthetic cytokine receptor, wherein the synthetic cytokine receptor comprises an extracellular domain, a transmembrane domain, and an interleukin 9 receptor (IL-9R) intracellular domain. [0009] In some embodiments, provided herein is a method of engineering an isolated cell, comprising contacting the cell with a polynucleotide encoding a synthetic cytokine receptor or a vector comprising such a polynucleotide, wherein the synthetic cytokine receptor comprises an extracellular domain, a transmembrane domain, and an interleukin 9 receptor (IL-9R) intracellular domain. [0010] In some embodiments, provided herein is an engineered cell expressing one or more synthetic cytokine receptors, wherein the synthetic cytokine receptor comprises an extracellular domain, a transmembrane domain, and an interleukin 9 receptor (IL-9R) intracellular domain. [0011] In some embodiments, provided herein is a population of cells, comprising at least one engineered cell expressing one or more synthetic cytokine receptors, wherein the synthetic cytokine receptor comprises an extracellular domain, a transmembrane domain, and an interleukin 9 receptor (IL-9R) intracellular domain. [0012] In some embodiments, provided herein is a pharmaceutical composition comprising an engineered cell expressing one or more synthetic cytokine receptors or a population of cells comprising at least one such engineered cell, wherein the synthetic cytokine receptor comprises an extracellular domain, a transmembrane domain, and an interleukin 9 receptor (IL-9R) intracellular domain. [0013] In some embodiments, provided herein is a method of treating a cancer in a subject, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition disclosed herein. [0014] In some aspects, provided herein is a synthetic cytokine receptor that is a homodimer of identical polypeptide chains each comprising an extracellular domain, a transmembrane domain, and an intracellular domain capable of interleukin 9 receptor (IL-9R) signaling. [0015] In some embodiments, the intracellular domain capable of IL-9R signaling comprises an IL-9R intracellular domain or a variant thereof. In some embodiments, the intracellular domain capable of IL-9R signaling comprises a chi