JP-2022532557-A5 -

Dates

Publication Date

20230515

Application Date

20200507

Description

In general, the terms used in the following claims should not be construed as limiting the claims to any specific embodiment disclosed herein or herein, but rather as encompassing all possible embodiments along with the full scope of the equivalents for which such claims are granted. Accordingly, the claims are not limited by this disclosure. In certain embodiments, for example, the following items are provided: (Item 1) A cell containing the first polynucleotide encoding MAGEA4 TCR, (a) The first polypeptide, (i) Extracellular TGFβ1 binding domain of TGFβR2, (ii) Transmembrane domain, and (iii) The first polypeptide, which includes an intracellular signaling domain for immune receptors, (b) polypeptide cleavage signal and (c) A second polypeptide, (i) Extracellular TGFβ1-binding domain of TGFβR1, (ii) Transmembrane domain, and A cell comprising a second polynucleotide encoding a fusion polypeptide, comprising a second polypeptide comprising an immune receptor intracellular signaling domain. (Item 2) The cell according to item 1, wherein the intracellular signaling domain of the first polypeptide is isolated from a cytokine receptor, interleukin receptor, pattern recognition receptor, or Toll-like receptor. (Item 3) The cell according to item 1 or item 2, wherein the intracellular signaling domain of the second polypeptide is isolated from a cytokine receptor, interleukin receptor, pattern recognition receptor, or Toll-like receptor. (Item 4) The cell according to item 1, wherein the intracellular signaling domain of the first polypeptide is an IL-12Rβ2 intracellular signaling domain, and the intracellular signaling domain of the second polypeptide is an IL-12Rβ1 intracellular signaling domain. (Item 5) The cell according to item 4, wherein the transmembrane domain of the first polypeptide comprises an IL-12Rβ2 transmembrane domain. (Item 6) The cell according to item 4 or item 5, wherein the transmembrane domain of the second polypeptide comprises an IL-12Rβ1 transmembrane domain. (Item 7) The cell according to item 1, wherein the intracellular signaling domain of the first polypeptide is an IL-12Rβ1 intracellular signaling domain, and the intracellular signaling domain of the second polypeptide is an IL-12Rβ2 intracellular signaling domain. (Item 8) The cell according to item 7, wherein the transmembrane domain of the first polypeptide comprises an IL-12Rβ1 transmembrane domain. (Item 9) The cell according to item 7 or item 8, wherein the transmembrane domain of the second polypeptide comprises an IL-12Rβ2 transmembrane domain. (Item 10) The cell according to item 1, wherein the intracellular signaling domain of the first polypeptide is an IL-7Rα intracellular signaling domain, and the intracellular signaling domain of the second polypeptide is an IL-2Rγ intracellular signaling domain. (Item 11) The cell according to item 10, wherein the transmembrane domain of the first polypeptide comprises an IL-7Rα transmembrane domain. (Item 12) The cell according to item 10 or item 11, wherein the transmembrane domain of the second polypeptide comprises an IL-2Rγ transmembrane domain. (Item 13) The cell according to item 1, wherein the intracellular signaling domain of the first polypeptide is an IL-2Rγ intracellular signaling domain, and the intracellular signaling domain of the second polypeptide is an IL-7Rα intracellular signaling domain. (Item 14) The cell according to item 13, wherein the transmembrane domain of the first polypeptide comprises an IL-2Rγ transmembrane domain. (Item 15) The cell according to item 13 or item 14, wherein the transmembrane domain of the second polypeptide comprises an IL-7Rα transmembrane domain. (Item 16) The cell according to item 1, wherein the intracellular signaling domain of the first polypeptide is an IL-2Rβ intracellular signaling domain, and the intracellular signaling domain of the second polypeptide is an IL-2Rγ intracellular signaling domain. (Item 17) The cell according to item 16, wherein the transmembrane domain of the first polypeptide comprises an IL-2Rβ transmembrane domain. (Item 18) The cell according to item 16 or item 17, wherein the transmembrane domain of the second polypeptide comprises an IL-2Rγ transmembrane domain. (Item 19) The cell according to item 1, wherein the intracellular signaling domain of the first polypeptide is an IL-2Rγ intracellular signaling domain, and the intracellular signaling domain of the second polypeptide is an IL-2Rβ intracellular signaling domain. (Item 20) The cell according to item 19, wherein the transmembrane domain of the first polypeptide comprises an IL-2Rγ transmembrane domain. (Item 21) The cell according to item 19 or item 20, wherein the transmembrane domain of the second polypeptide comprises an IL-2Rβ transmembrane domain. (Item 22) The cell according to item 1, wherein the intracellular signaling domain of the first polypeptide is an IL-21R intracellular signaling domain, and the intracellular signaling domain of t