Disclosed are compositions neoantigens and T cell receptors (TCRs) specific for one or more neoantigens as well as methods of their use for treating cancer.

Disclosed are compositions and methods for targeted treatment of myeloid and B cell malignancies. In particular, chimeric antigen receptor (CAR) T cells are disclosed that can be used with adoptive cell transfer to target and kill myeloid and B cell malignancies with reduced antigen escape. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a myeloid and B cell malignancies that involves adoptive transfer of the disclosed CAR T cells.

There is described herein a method for improving the anti-cancer properties of T-cells, the method comprising: providing a population of T-cells; and culturing the T-cells in an environment that activates the GCN2 pathway.

The present invention provides compositions and methods for inhibiting one or more diacylglycerol kinase (DGK) isoform in a cell in order to enhance the cytolytic activity of the cell. In one embodiment, the cells may be used in adoptive T cell transfer. For example, in some embodiments, the cell is modified to express a chimeric antigen receptor (CAR). Inhibition of DGK in T cells used in adoptive T cell transfer increases cytolytic activity of the T cells and thus may be used in the treatment of a variety of conditions, including cancer, infection, and immune disorders.

The present disclosure relates to compositions and methods for compositions, methods, and kits for treating cancer using chimeric antigen receptor (CAR) modified cells. Some embodiments of the present disclosure relate to an isolated nucleic acid sequence encoding CAR. The CAR may include an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain. The antigen binding domain may bind to an antigen of a non-essential organ.

The presently disclosed subject matter provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to novel designs of chimeric antigen receptors (CARs) and engineered immunoresponsive cells comprising the same. The engineered immunoresponsive cells comprising the novel CARs are antigen-directed and have extended persistence without compromising function.

Described herein are T cells engineered to express a chimeric antigen receptor (CAR), such as an anti-mesothelin CAR alone or in combination with a follicle-stimulating hormone receptor (FSHR) binding domain and/or a dominant negative transforming growth factor-? receptor II (dnTGF?RII) for the treatment of diseases associated with mesothelin expression. Also described are T cells engineered to express a modified T cell receptor (TCR).

The present invention discloses a novel switchable dual chimeric antigen receptor-T (sdCAR-T) cell and a construction method and use thereof, which fall within the field of cellular immunotherapy for tumors. The dual chimeric antigen receptor consists of a first chimeric antigen receptor for MSLN and a second chimeric antigen receptor for FITC. A dual-targeted functional T cells regulated by specific exogenous bifunctional molecules is constructed, and the exogenous molecules are used to preliminarily discuss the in vivo and in vitro activity of the dual chimeric antigen receptor-T cell. By means of in vitro and in vivo tests, it is confirmed that the activation mode of the constructed CAR-T cell is controlled by the combination of endogenous tumor antigens and exogenous bifunctional molecules, and this combined regulation mode can significantly improve the safe application of CAR-T cell immunotherapy.

The disclosure features amphiphilic ligand conjugates comprising a chimeric antigen receptor (CAR)ligand and a lipid. The disclosure also features compositions and methods of using the same, for example, to stimulate proliferation of CAR expressing cells.

The invention provides methods of increasing the efficacy of a T cell therapy in a patient in need thereof. The invention includes methods of identifying a patient who would respond well to a T cell therapy or conditioning a patient prior to a T cell therapy so that the patient responds well to a T cell therapy. The conditioning involves administering one or more preconditioning agents prior to a T cell therapy and identifying biomarker cytokines prior to administering a T cell therapy.