Disrupting convergence of lytic granules produced by cytotoxic lymphocytes allows non-directional degranulation, which improves and broadens killing efficiency of the cytotoxic cells in pathogenic environments such as when used for cancer therapy. Accordingly, methods of inducing multidirectional degranulation by cytotoxic effector cells in a tumor microenvironment, methods of treating a tumor, and related therapeutic composition are described.

The disclosure provides therapeutic combinations of chimeric antigen receptor T cells that specifically bind human STEAP2 (e.g., AZD0754) with androgen receptor antagonists (e.g., enzalutamide). Methods of administering the combinations to treat cancer (e.g., prostate cancer) are also provided.

The present disclosure provides gene edited modified immune cells or precursors thereof (e.g., gene edited modified T cells) comprising an exogenous T cell receptor (TCR) and/or a chimeric antigen receptor (CAR) having specificity for a target antigen, and an insertion and/or deletion in one or more endogenous gene loci, wherein the endogenous gene loci encode regulators of T cell function, thereby resulting in immune cells having enhanced function. Compositions and methods of treatment are also provided. The present invention provides methods of screening for TCR- or CAR-T cells with enhanced immune function (e.g., T cell efficacy, T cell memory, and/or T cell persistence).

The disclosure provides novel antigen-binding proteins that bind STEAP1 and methods of use.

The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing at least one of an antigen recognizing receptor and one of a chimeric costimulatory receptor. Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

The present invention relates to compositions and methods for generating a modified T cell with a nucleic acid capable of downregulating endogenous gene expression selected from the group consisting of TCR chain, TCR chain, beta-2 microglobulin, a HLA molecule, CTLA-4, PD1, and FAS and further comprising a nucleic acid encoding a modified T cell receptor (TCR) comprising affinity for a surface antigen on a target cell or an electroporated nucleic acid encoding a chimeric antigen receptor (CAR). Also included are methods and pharmaceutical compositions comprising the modified T cell for adoptive therapy and treating a condition, such as an autoimmune disease.

The present disclosure provides gene edited modified immune cells or precursors thereof (e.g., gene edited modified T cells) comprising an exogenous T cell receptor (TCR) and/or a chimeric antigen receptor (CAR) having specificity for a target antigen, and an insertion and/or deletion in one or more endogenous gene loci, wherein the endogenous gene loci encode regulators of T cell function, thereby resulting in immune cells having enhanced function. Compositions and methods of treatment are also provided. The present invention provides methods of screening for TCR- or CAR-T cells with enhanced immune function (e.g., T cell efficacy, T cell memory, and/or T cell persistence).

The present invention relates to engineered T-cell(s) and methods for using the same as a therapeutic with a potent and selective ability to target an antigen of choice. Engineered T-cells of the disclosure are useful in the treatment of various cancers, infectious diseases, and immune disorders. Also disclosed are methods for expanding engineered and non-engineered T-cell(s) populations to therapeutically useful quantities. An engineered T-cell of the disclosure can be a universal donor, and can be administered to a subject with any MHC haplotype.

Nucleic acid molecules encoding an IL-15 domain and a chimeric antigen receptor (CAR) that targets cells expressing prostate stem cell antigen (PSCA) are provided as well as polypeptides encoded thereby. Vectors and immune cells (e.g., NKT cells) containing the nucleic acid molecules also are disclosed, as well as methods for their use.

The technology relates generally to the field of immunology and relates in part to T cell compositions and methods for treating diseases and disorders associated with the presence of tumor cells that express prostate stem cell antigen.