Mucosal-associated invariant t (MAIT) cells expressing chimeric antigen receptors
The present invention relates generally to immunotherapy, in particular immunotherapy for treating cancer, infectious diseases or autoimmune diseases. More specifically, the invention relates to Mucosal-Associated Invariant T (MAIT) cells expressing Chimeric Antigen Receptors (CARs), wherein the MAIT cell is allogenic with respect to the subject to be treated.
1 . A method of treating a cancer, an autoimmune disease or an infectious disease in a subject in need thereof, comprising
administering to the subject a therapeutically effective amount of mucosa associated invariant T (MAIT) cells expressing a chimeric antigen receptor (CAR),
wherein the MAIT cells are transduced in order to express the CAR, and
wherein the MAIT cells are allogenic with respect to the subject and do not induce graft versus host disease in the subject.
2 . The method according to claim 1 , wherein the cancer is a hematologic malignancy.
3 . The method according to claim 1 , wherein the cancer is a solid tumor.
4 . The method according to claim 1 , wherein the subject is an immunocompromised subject.
5 . The method according to claim 1 , wherein the MAIT cells are administered after a conditioning treatment, rendering the subject immunocompromised.
6 . The method according to claim 5 , wherein the conditioning treatment is chemotherapy, radiotherapy and/or administration of lymphodepleting antibodies.
7 . The method according to claim 1 , wherein the CAR specifically binds to a tumor-associated antigen (TAA).
8 . The method according to claim 1 , wherein the CAR specifically binds to a TAA expressed at the surface of tumor cells.
9 . The method according to claim 1 , wherein the CAR specifically targets an intracellular oncoprotein, a self-reactive antibody, or an intracellular tumor-associated antigen.
10 . The method according to claim 3 , wherein the cancer is selected from the group consisting of: breast cancer, prostate cancer, ovarian cancer, cervical cancer, skin cancer, pancreatic cancer, colorectal cancer, renal cancer, liver cancer, brain cancer, and lung cancer.
11 . The method of claim 1 , wherein the MAIT cells are administered prior to a transplant of hematopoietic stem cells (HSC) or after a transplant of hematopoietic stem cells (HSC).
12 . The method of claim 8 , wherein the TAA is selected from the group consisting of CD19, GD2, EGFR, CD20, CD22, CD33, CD138, CD52, CD30, ROR1, HER2, EpCAM, MUC-1, MUC5AC, BCMA, CD38, SLAMF7/CS1, CD123, IL-13Ra2, LeY, MUC16 and PSMA.
13 . The method of claim 12 , wherein the TAA is CD19, CD20, CD22, CD33, CD138, BCMA, CD38, SLAMF7/CS1, IL-13Ra2 or HER2.
14 . The method of claim 9 , wherein the intracellular tumor-associated antigen is WT-1, NY-ESO-1, MAGE, PRAME, RAS, mesothelin, c-Met, CEA, CSPG-4, EBNA3C, CA-125 or GPA7.
15 . The method of claim 1 , further comprising activating the MAIT cells in the presence of a stimulatory agent prior to the administering step, wherein the stimulatory agent is not 5-OP-RU.
16 . The method of claim 1 , wherein the method is for treating an autoimmune disease.