Method to Treat Cancer with Engineered T-Cells

• US 20190134091A1
• Filed: 06/12/2016
• Published: 05/09/2019
• Est. Priority Date: 06/12/2015
• Status: Active Grant

• Current Assignee: Lentigen Technology Inc. (Miltenyi GmbH)
• Original Assignee: Lentigen Technology Inc. (Miltenyi GmbH)
• Inventors: Dropulic, Boro, Orentas, Rimas, Schneider, Dina, Krueger, Winfried
• Granted Patent: US 10,639,329 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 38/177 Receptors; Cell surface antigens; Cell surface determinants
• CPC Class Codes: A61K 38/1774 Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4631 Chimeric Antigen Receptors [CAR]
• CPC Class Codes: A61K 39/4632 T-cell receptors [TCR]; antibody T-cell receptor constructs
• CPC Class Codes: A61K 39/464499 Undefined tumor antigens, e.g. tumor lysate or antigens targeted by cells isolated from tumor
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C07K 14/7051 T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 2319/03 containing a transmembrane segment
• CPC Class Codes: C12N 2502/1121 Dendritic cells
• CPC Class Codes: C12N 2510/00 Genetically modified cells
• CPC Class Codes: C12N 2740/16043 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 5/0636 T lymphocytes

Abstract

Novel adoptive immunotherapy compositions comprising co-cultured lentiviral vector-transduced autologous antigen presentation cells and T cells are provided herein as well as are methods of use of same in a patient-specific combination immunotherapy that can be used to treat cancers and other diseases and conditions.

Claims

1. An adoptive immunotherapy composition comprising an autologous T-cell population transduced with one or more lentiviral vectors encoding single or multiple chimeric antigen receptors (CARs), wherein the T cells are co-cultured with autologous antigen presentation cells transduced with one or more lentiviral vectors expressing patient-derived tumor antigens thereby generating an active patient-specific autologous anti-tumor T-cell population capable of promoting in vivo expansion, persistence of patient-specific anti-tumor T-cells resulting in tumor stabilization, reduction, and/or elimination, and/or remission and/or elimination of cancer in a patient-specific manner.

2. The adoptive immunotherapy composition of claim 1, wherein the T-cell population is additionally transduced with one or more lentiviral vectors encoding tumor-specific T-cell receptors (TCRs).

11. The adoptive immunotherapy composition of claim 1, wherein the CAR comprises at least one extracellular antigen binding domain, at least one linker domain, at least one transmembrane domain, and at least one intracellular signaling domain.

12. The adoptive immunotherapy composition of claim 11, wherein the at least one extracellular antigen binding domain of the CAR comprises at least one single chain variable fragment of an antibody that binds to the antigen or at least one heavy chain variable region of an antibody that binds to the antigen.

16. The adoptive immunotherapy composition of claim 11, wherein the at least one extracellular antigen binding domain of the CAR targets an antigen comprising CD19, CD20, CD22, ROR1, TSLPR, mesothelin, CD33, CD38, CD123 (IL3RA), CD138, BCMA (CD269), GPC2, GPC3, FGFR4, c-Met, PSMA, Glycolipid F77, EGFRvIII, GD-2, NY-ESO-1 TCR, MAGE A3 TCR, or any combination thereof.

17. The adoptive immunotherapy composition of claim 11, wherein the at least one extracellular antigen binding domain of the CAR comprises an anti-CD19 scFV antigen binding domain, an anti-CD20 scFV antigen binding domain, an anti-CD22 scFV antigen binding domain, an anti-ROR1 scFV antigen binding domain, an anti-TSLPR scFV antigen binding domain, an anti-mesothelin scFV antigen binding domain, an anti-CD33 scFV antigen binding domain, an anti-CD38 scFV antigen binding domain, an anti-CD123 (IL3RA) scFV antigen binding domain, an anti-CD138 scFV antigen binding domain, an anti-BCMA (CD269) scFV antigen binding domain, an anti-GPC2 scFV antigen binding domain, an anti-GPC3 scFV antigen binding domain, an anti-FGFR4 scFV antigen binding domain, an anti-c-Met scFV antigen binding domain, an anti-PMSA scFV antigen binding domain, an anti-glycolipid F77 scFV antigen binding domain, an anti-EGFRvIII scFV antigen binding domain, an anti-GD-2 scFV antigen binding domain, an anti-NY-ESo-1 TCR scFV antigen binding domain, an anti-MAGE A3 TCR scFV antigen binding domain, or an amino acid sequence with 85%, 90%, 95%, 96%, 97%, 98% or 99% identity thereof, or any combination thereof.

19. The adoptive immunotherapy composition of claim 11, wherein the at least one transmembrane domain comprises a transmembrane domain of a protein selected from the group consisting of the alpha, beta or zeta chain of the T-cell receptor, CD28, CD3 epsilon, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, CD154, CD271, TNFRSF19, or any combination thereof.

20. The adoptive immunotherapy composition of claim 11, wherein the at least one intracellular signaling domain comprises a CD3 zeta intracellular domain.

22. The adoptive immunotherapy composition of claim 11, wherein the at least one intracellular signaling domain comprises a costimulatory domain, a primary signaling domain, or any combination thereof.

23. The adoptive immunotherapy composition of claim 11, wherein the at least one costimulatory domain comprises a functional signaling domain of OX40, CD70, CD27, CD28, CD5, ICAM-1, LFA-1 (CD11a/CD18), ICOS (CD278), DAP10, DAP12, and 4-1BB (CD137), or any combination thereof.

27. The adoptive immunotherapy composition of claim 1, wherein the T cells are T cells of a human having cancer.

28. The adoptive immunotherapy composition of claim 1, wherein the cancer is a hematological cancer, and wherein the hematological cancer is leukemia, lymphoma, or multiple myeloma.

29. The adoptive immunotherapy composition of claim 28, wherein the leukemia is chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), or chronic myelogenous leukemia (CIVIL).

30. The adoptive immunotherapy composition of claim 28, wherein the lymphoma is mantle cell lymphoma, non-Hodgkin'"'"'s lymphoma or Hodgkin'"'"'s lymphoma.

32. The adoptive immunotherapy composition of claim 27, wherein the cancer includes an adult carcinoma comprising oral and pharynx cancer (tongue, mouth, pharynx, head and neck), digestive system cancers (esophagus, stomach, small intestine, colon, rectum, anus, liver, intrahepatic bile duct, gallbladder, pancreas), respiratory system cancers (larynx, lung and bronchus), bones and joint cancers, soft tissue cancers, skin cancers (melanoma, basal and squamous cell carcinoma), pediatric tumors (neuroblastoma, rhabdomyosarcoma, osteosarcoma, Ewing'"'"'s sarcoma), tumors of the central nervous system (brain, astrocytoma, glioblastoma, glioma), and cancers of the breast, the genital system (uterine cervix, uterine corpus, ovary, vulva, vagina, prostate, testis, penis, endometrium), the urinary system (urinary bladder, kidney and renal pelvis, ureter), the eye and orbit, the endocrine system (thyroid), and the brain and other nervous system, or any combination thereof.

3-10. -10. (canceled)

13-15. -15. (canceled)

18. (canceled)

21. (canceled)

24-26. -26. (canceled)

31. (canceled)

33. A method of treating a mammal having a solid tumor, the method comprising administering to the subject a pharmaceutical composition comprising an anti-tumor effective amount of an autologous T-cell population transduced with one or more lentiviral vectors encoding single or multiple chimeric antigen receptors (CARs), wherein the one or more lentiviral vectors encode an anti-CD19, an anti-CD20, or an anti-CD22 chimeric antigen receptor, wherein the T-cells are co-cultured with autologous monocyte-derived dendritic cells transduced with one or more lentiviral vectors expressing patient-derived tumor antigens, thereby generating an active patient-specific autologous anti-tumor T-cell population capable of promoting in vivo expansion, persistence of patient-specific anti-tumor T-cells resulting in tumor stabilization, reduction, and/or elimination, and/or remission and/or elimination of cancer in a patient-specific manner.

34. The method of claim 33, wherein the T-cell population is additionally transduced with one or more lentiviral vectors encoding tumor-specific T-cell receptors (TCRs) thereby generating an active patient-specific autologous anti-tumor T-cell population capable of recognizing said tumor-specific T-cell receptors (TCRs) which can be infused directly back into the patient to promote in vivo expansion, persistence of patient-specific anti-tumor T-cells resulting in tumor stabilization, reduction, and/or elimination, and/or remission and/or elimination of cancer in a patient-specific manner.

36. The method of claim 34, wherein the T cell has been preselected by virtue of expressing specific activation or memory-associated surface markers.

37. The method of claim 34, wherein the T cell and dendritic cells are derived from a hematopoietic stem cell donor, and wherein the procedure is carried out in the context of hematopoietic stem cell transplantation.

35. A method of treating a mammal having a solid tumor, the method comprising administering to the subject a pharmaceutical composition comprising an anti-tumor effective amount of an autologous T-cell population transduced with one or more lentiviral vectors encoding single or multiple chimeric antigen receptors (CARs), wherein the one or more lentiviral vectors encode an anti-CD19, an anti-CD20, or an anti-CD22 chimeric antigen receptor, wherein the T-cell population is additionally transduced with one or more lentiviral vectors encoding tumor-specific T-cell receptors (TCRs) to generate an active patient-specific autologous anti-tumor T-cell population capable of recognizing said tumor-specific T-cell receptors (TCRs) which can be infused directly back into the patient to promote in vivo expansion, persistence of patient-specific anti-tumor T-cells resulting in tumor stabilization, reduction, and/or elimination, and/or remission and/or elimination of cancer in a patient-specific manner.