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

Provided herein are T-cell receptor (TCR) fusion proteins (TFPs), T-cells engineered to express one or more TFPs, and methods of use thereof for the treatment of diseases, including cancer.

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.

The present invention refers to a bispecific in tandem receptor CAR, named RfuCAR, which includes a scFv that recognizes and ligates surface molecules on tumoral cells (CD33, CD123 or another tumoral target) and the IL-1 receptor type 2 (IL-1R2). According to this, the IL1-R2 was chosen as the ideal receptor to compose the RfuCAR construction, being able to capture the IL-103 with high affinity and specificity. These proprieties indicate it as a good candidate to reduce the neurotoxicity and CRS effects of CAR-T therapies. Additionally, the present invention deals with a method for modulating the tumoral microenvironment, for example, in case of acute myeloid leukemia, or other cancer type like but not restricted to acute lymbloblastic leukemia, pancreatic, lung and ovarian cancer.

Mesothelin-specific binding proteins including mesothelin-specific T cell receptor (TCR) that specifically binds to mesothelin including. for example. in a complex with an MHC. Methods of making and using the mesothelin-specific binding proteins are also described, including the use of the mesothelin-specific binding protein in adoptive cell therapy.

The invention relates to methods for expanding ?? T cells comprising preparing a composition enriched for ?? T cells and culturing the composition in the presence of feeder cells. Also provided is a method for engineering ?? T cells comprising preparing a composition enriched for ?? T cells, transducing the composition to express a chimeric antigen receptor (CAR) specific for a tumour associated antigen and culturing the transduced composition to expand the engineered ?? T cells. Also provided are expanded and engineered ?? T cells produced according to the described methods, which find utility in adoptive T cell therapies, chimeric receptor therapies and the like.

The presently disclosed subject matter provides for chimeric receptors that target MUC16 and cells comprising such chimeric receptors. The presently disclosed subject matter further provides uses of the chimeric receptors for treatment.

Provided are compositions and methods for treating diseases associated with expression of mesothelin. Also provided are a chimeric antigen receptor (CAR) specific to mesothelin, vectors encoding the same, and recombinant T cells comprising the mesothelin CAR. Further provided are methods of administering a genetically modified T cell expressing a CAR that comprises a mesothelin binding domain.

The invention includes compositions comprising at least one chimeric autoantibody receptor (CAAR) specific for an autoantibody, vectors comprising the same, compositions comprising CAAR vectors packaged in viral particles, and recombinant T cells comprising the CAAR. The invention also includes methods of making a genetically modified T cell expressing a CAAR (CAART) wherein the expressed CAAR comprises a desmoglein extracellular domain.