The present disclosure provides improved genome editing compositions and methods for editing a PD-1 gene. The disclosure further provides genome edited cells for the prevention, treatment, or amelioration of at least one symptom of, a cancer, an infectious disease, an autoimmune disease, an inflammatory disease, or an immunodeficiency.

The presently disclosed subject matter provides uses of a chimeric costimulatory receptor (CCR) targeting CD38, and cells comprising a CD38 CCR and an antigen-recognizing receptor, and uses of such cells.

The presently disclosed subject matter provides for methods and compositions for treating multiple myeloma. It relates to chimeric antigen receptors (CARs) that specifically target B cell maturation antigen (BCMA), and immunoresponsive cells comprising such CARs. The presently disclosed BCMA-specific CARs have enhanced immune-activating properties, including anti-tumor activity.

Provided herein are chimeric antigen receptors (CARs), such as those specific for BCMA, that have improved properties, including increased CAR T cell binding to BCMA and improved CAR T cell killing of BCMA-expressing cancer cells. Use of the CARs in immune cells (e.g., T cells), compositions (e.g., CARs and nucleic acid constructs encoding the same), and methods are also contemplated.

The present disclosure relates to compositions and methods for predicting cancer survival or toxicity in a subject receiving a chimeric antigen receptor (CAR) T cell therapy. The present disclosure further discloses compositions, e.g., pharmaceutical compositions, and methods for treating said subject.

The present disclosure provides a TCR-T cell for tumor-killing, wherein the TCR-T cell is a T cell carrying a TCR that recognizes a tumor antigen, and the TCR in the TCR-T cell is derived from any one or more of the following T cells: 1) a CD4 T cell expressing one or more of TNFRSF18, CXCL13, TNFRSF4, TNFSF8, ENTPD1, ACP5, LAYN, TNFRSF9, CTLA4, CD200 and TIGIT genes in the tumor; and 2) a CD8 T cell expressing one or more of TNFRSF18, CXCL13, CXCR6, GALNT2, ENTPD1, ACP5, HAVCR2, LAYN, TNFRSF9, CTLA4 and CD109 genes in the tumor. The TCR-T cell according to the present disclosure can be effectively applied to the treatment of a tumor, especially in an immunotherapy.

The invention provides compositions and methods improved CAR T cell therapies. Specifically, the invention provides cells with reduced Tet, e.g., Tet2 function or expression, and methods of use therefore. The invention further provides Tet2 inhibitors and methods of use therefore in connection with CAR T cells.

The invention relates to cancer therapeutics, in particular, the system of making cancer cells more susceptible to effector cells by introduction of cellular therapy targets into the cancer cells.

The present disclosure relates to the identification and use of biomarkers (e.g., analytes, analyte profiles, or markers (e.g., gene expression and/or protein expression profiles)) with clinical relevance to cytokine release syndrome (CRS).

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.