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US-20260125449-A1 - ARTICLES OF MANUFACTURE AND METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY

US20260125449A1US 20260125449 A1US20260125449 A1US 20260125449A1US-20260125449-A1

Abstract

Provided are adoptive cell therapy methods involving the administration of doses of cells for treating disease and conditions, including certain B cell malignancies. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs). In some embodiments, the methods are for treating subjects with non-Hodgkin lymphoma (NHL). In some embodiments, the methods are for treating subjects with relapsed or refractory NHL. Also provided are articles of manufacture and prophylactic treatments in connection with adoptive therapy methods.

Inventors

  • Tina Albertson
  • Brian CHRISTIN
  • Jacob Randolph GARCIA
  • Christopher Glen RAMSBORG
  • Claire L. SUTHERLAND
  • Clinton WEBER
  • Rachel K. YOST
  • Mark J. Gilbert
  • He Li

Assignees

  • JUNO THERAPEUTICS, INC.

Dates

Publication Date
20260507
Application Date
20251107

Claims (20)

  1. 1 . A method of treating a subject having a lymphoma associated with central nervous system (CNS) involvement, the method comprising administering to a subject a dose of T cells comprising T cells expressing a chimeric antigen receptor (CAR) that specifically binds to CD19.
  2. 2 . The method of claim 1 , wherein the subject has a brain lesion.
  3. 3 . The method of claim 1 , wherein the subject has a temporal lobe brain lesion.
  4. 4 . The method of claim 1 , wherein the lymphoma is non-Hodgkin lymphoma (NHL).
  5. 5 . The method of claim 1 , wherein the subject has relapsed following remission after treatment with, or become refractory to, one or more prior lines of therapies.
  6. 6 . The method of claim 1 , wherein the subject has relapsed following remission after treatment with, or become refractory to, two or more prior lines of therapy.
  7. 7 . The method of claim 1 , wherein the CAR comprises an scFv specific for CD19, a transmembrane domain, a cytoplasmic signaling domain derived from a costimulatory molecule, a cytoplasmic signaling domain that comprises a CD3zeta signaling domain, and a spacer between the transmembrane domain and the scFv.
  8. 8 . The method of claim 7 , wherein the scFv specific for CD19 is derived from FMC63.
  9. 9 . The method of claim 7 , wherein the costimulatory molecule is 4-1BB.
  10. 10 . The method of claim 8 , wherein the costimulatory molecule is 4-1BB.
  11. 11 . The method of claim 1 , wherein the dose of T cells comprises between at or about 2.5×10 7 viable CAR-expressing T cells and at or about 2×10 8 viable CAR-expressing T cells, inclusive.
  12. 12 . The method of claim 1 , wherein the dose of T cells comprises between at or about 5×10 7 viable CAR-expressing T cells and at or about 1×10 8 viable CAR-expressing T cells, inclusive.
  13. 13 . The method of claim 1 , wherein the dose of T cells comprises a ratio of CAR-expressing CD4+ T cells to CAR-expressing CD8+ T cells, the ratio comprising between at or about 5:1 and at or about 1:5.
  14. 14 . The method of claim 12 , wherein the dose of T cells comprises a ratio of CAR-expressing CD4+ T cells to CAR-expressing CD8+ T cells, the ratio comprising between at or about 5:1 and at or about 1:5.
  15. 15 . The method of claim 14 , wherein the ratio of the CAR-expressing CD4+ T cells to CAR-expressing CD8+ T cells is about 1:1.
  16. 16 . The method of claim 1 , wherein administering the dose of T cells comprises administering a plurality of separate compositions, the plurality of separate compositions comprising a first composition comprising one of CD4+ T cells and CD8+ T cells and a second composition comprising the other of the CD4+ T cells and the CD8+ T cells.
  17. 17 . The method of claim 1 , wherein: the dose of T cells comprises between at or about 5×10 7 viable CAR-expressing T cells and at or about 1×10 8 viable CAR-expressing T cells, inclusive; and the CAR comprises an scFv specific for CD19, a transmembrane domain, a cytoplasmic signaling domain derived from a 4-1BB costimulatory molecule, a cytoplasmic signaling domain that comprises a CD3zeta signaling domain, and a spacer between the transmembrane domain and the scFv.
  18. 18 . The method of claim 17 , wherein administering the dose of T cells comprises administering a plurality of separate compositions, the plurality of separate compositions comprising a first composition comprising one of CD4+ T cells and CD8+ T cells and a second composition comprising the other of the CD4+ T cells and the CD8+ T cells.
  19. 19 . A method of treating a subject having a lymphoma associated with central nervous system (CNS) involvement, the method comprising administering to a subject a dose of T cells comprising T cells expressing a chimeric antigen receptor (CAR) that specifically binds to CD19, wherein: the dose of T cells comprises between at or about 2.5×10 7 viable CAR-expressing T cells and at or about 2×10 8 viable CAR-expressing T cells, inclusive; and the lymphoma is non-Hodgkin lymphoma (NHL).
  20. 20 . The method of claim 19 , wherein the dose of T cells comprises between at or about 5×10 7 viable CAR-expressing T cells and at or about 1×10 8 viable CAR-expressing T cells, inclusive.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS The application is a continuation of U.S. application Ser. No. 18/882,479, filed Sep. 11, 2024, which is a continuation of U.S. application Ser. No. 18/510,460, filed Nov. 15, 2023, which is a continuation of U.S. application Ser. No. 17/846,868, filed Jun. 22, 2022, now issued as U.S. Pat. No. 11,944,647, which is a continuation of U.S. application Ser. No. 16/616,938, filed Nov. 25, 2019, now issued as U.S. Pat. No. 11,413,310, which is a National Stage application under 35 U.S.C. § 371 of International Application No. PCT/US2018/035755, filed Jun. 1, 2018, which claims priority from U.S. provisional application No. 62/514,774, filed Jun. 2, 2017, entitled “ARTICLES OF MANUFACTURE AND METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY,” U.S. provisional application No. 62/515,530, filed Jun. 5, 2017, entitled “ARTICLES OF MANUFACTURE AND METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY,” U.S. provisional application No. 62/521,366, filed Jun. 16, 2017, entitled “ARTICLES OF MANUFACTURE AND METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY,” U.S. provisional application No. 62/527,000, filed Jun. 29, 2017, entitled “ARTICLES OF MANUFACTURE AND METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY,” U.S. provisional application No. 62/549,938, filed Aug. 24, 2017, entitled “ARTICLES OF MANUFACTURE AND METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY,” U.S. provisional application No. 62/580,425, filed Nov. 1, 2017, entitled “ARTICLES OF MANUFACTURE AND METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY,” U.S. provisional application No. 62/593,871, filed Dec. 1, 2017, entitled “ARTICLES OF MANUFACTURE AND METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY,” U.S. provisional application No. 62/596,764, filed Dec. 8, 2017, entitled “ARTICLES OF MANUFACTURE AND METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY,” U.S. provisional application No. 62/614,957, filed Jan. 8, 2018, entitled “ARTICLES OF MANUFACTURE AND METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY,” the contents of which are incorporated by reference in their entirety. INCORPORATION BY REFERENCE OF SEQUENCE LISTING The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled 735042012104SeqList.xml, created Nov. 4, 2025, which is 75,565 bytes in size. The information in the electronic format of the Sequence Listing is incorporated by reference in its entirety. FIELD The present disclosure relates in some aspects to adoptive cell therapy involving the administration of doses of cells for treating subjects with disease and conditions such as certain B cell malignancies, and related methods, compositions, uses and articles of manufacture. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs). In some embodiments, the disease or condition is a non-Hodgkin lymphoma (NHL), such as relapsed or refractory NHL or specific NHL subtype; in some embodiments, the subject is of a specific group or subset of NHL subjects, such as heavily pretreated or poor-prognosis subjects. BACKGROUND Various immunotherapy and/or cell therapy methods are available for treating diseases and conditions. For example, adoptive cell therapies (including those involving the administration of cells expressing chimeric receptors specific for a disease or disorder of interest, such as chimeric antigen receptors (CARs) and/or other recombinant antigen receptors, as well as other adoptive immune cell and adoptive T cell therapies) can be beneficial in the treatment of cancer or other diseases or disorders. Improved approaches are needed. Provided are methods and uses that meet such needs. SUMMARY Provided herein are methods, uses, compositions, formulations and articles of manufacture for treating subjects having or suspected of having a disease or condition, such as a cancer or tumor, optionally a B cell malignancy such as NHL or ALL or CLL or a subtype thereof. The methods and other embodiments generally relate to administering to the subject T cells, generally engineered T cells, such as those expressing or containing a recombinant receptor such as a chimeric antigen receptor (CAR) or TCR. In some embodiments, the dose of cells or cells administered in connection with any embodiments of the provided methods, compositions, articles of manufacture and uses, contains CD4+ T cells or a subtype or phenotype thereof (such as engineered or recombinant receptor-expressing CD4+ T cells) and/or CD8+ T cells or a subtype thereof (such as an engineered or recombinant receptor-expressing CD4+ cells). In some embodiments, the CD8+ cells or subtype or phenotype are present at a particular dose or amount or number; in some embodiments the CD4+ cells or subtype or phenotype are present at a particular dose or amount or number. In some embodiments, the CD8+ cells or subtype or phenotype thereof and the CD4+ cells or subtype or phenotype thereof, ar