Disclosed herein are methods for treating cancer comprising administering CAR-modified immune cells and at least one Retinoic Acid Receptor and/or Retinoid X Receptor active agent.

Disclosed herein are methods for treating cancer comprising administering CAR-modified immune cells and at least one Retinoic Acid Receptor and/or Retinoid X Receptor active agent.

Chimeric receptors are provided. Accordingly, there is provided a chimeric receptor comprising an extracellular binding domain and a heterologous amino acid sequence capable of recruiting a co-receptor comprising an intracellular signaling domain, such that upon binding of the extracellular binding domain to its target the signaling is transmitted in a cell expressing the chimeric receptor and the co-receptor. Also provided are protein complexes comprising the receptors, cells expressing same and uses thereof.

The present invention relates to chimeric antigen receptor (CAR)-T cells, and particularly, although not exclusively, to anti-T-cell receptor (TCR) V-beta CARs, and to their use in immunotherapy, and for treating, preventing or ameliorating cancer, such as T-cell lymphomas, various microbial infections, such as HIV and TB, and also autoimmune disease. The invention is especially concerned with the use of CAR-engineered mucosal-associated invariant T (MAIT) cells, and to novel methods for stimulating, isolating and expanding highly purified MAIT cells, which can then be engineered into such CAR-MAIT cells. The invention extends to genetic constructs per se, and to their use in generating the CAR-MAIT cells, and to transduced CAR-MAIT cells per se. The invention also extends to various medical uses of the constructs and transduced CAR-MAIT cells, and to pharmaceutical compositions comprising these constructs and CAR-MAIT cells.

The present invention relates to chimeric antigen receptor (CAR)-T cells, and particularly, although not exclusively, to their use in immunotherapy, and for treating, preventing or ameliorating cancer, such as T-cell lymphomas, various microbial infections, such as HIV and TB, and also autoimmune disease. The invention is especially concerned with the use of CAR-engineered mucosal-associated invariant T (MAIT) cells, and to novel methods for stimulating, isolating, and expanding highly purified MAIT cells, which can then be engineered into such CAR-MAIT cells. The invention is also concerned with methods for expansion of MAIT cells in vitro.

The present invention provides compositions comprising chimeric receptors, including chimeric costimulatory receptors (CCRs), and/or chemokine receptors, methods for preparing CCRs and/or chemokine receptors, and therapeutic populations of tumor infiltrating lymphocytes, marrow infiltrating lymphocytes, and peripheral blood lymphocytes expressing CCRs and/or chemokine receptors with increased therapeutic performance and other advantages for the treatment of cancers, including solid tumor cancers.

The present disclosure relates to methods and compositions to confer and/or increase immune responses mediated by cellular immunotherapy, such as by adoptively transferring tumor-specific genetically-modified lymphocytes such as human T lymphocytes. The disclosure provides compositions comprising genetically-modified lymphocytes that express at least two transgene(s) having the ability to modulate the immune system and the innate and adaptive immune response.

Disclosed are compositions and methods for preventing graft versus host disease (GVHD) in subjects receiving donor cells. In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to suppress alloreactive donor cells. Therefore, also disclosed are methods of suppressing alloreactive donor cells in a subject receiving transplant donor cells that involves adoptive transfer of the disclosed regulatory T cells engineered to express the disclosed CARs. Also disclosed is a method of preventing rejection of off-the-shelf therapeutic immune effector cells, such as CAR-T cells, in a subject that involves administering to the subject an effective amount of a regulatory T cell genetically modified with a disclosed CD83-specific CAR.

The presently disclosed subject matter provides for antigen-recognizing receptors that specifically target CD33 and cells comprising such CD33-targeted antigen-recognizing receptors. The presently disclosed subject matter further provides uses of the CD33-targeted antigen-recognizing receptors for treatment.

Disclosed herein is a chimeric antigen receptor (CAR) comprising a single-chain variable fragment specific to Globo H, a hinge and transmembrane domain, a co-stimulatory molecule, and a cytoplasmic domain. According to some embodiments of the present disclosure, the CAR further comprises a single-chain variable fragment specific to PD-L1, and optionally, a fragment crystallizable region of an immunoglobulin. Also disclosed herein are isolated nucleic acids encoding the CAR pharmaceutical kits comprising the isolated immune cells expressing the CAR, and methods of treating cancers by using isolated immune cells.