The present invention is directed to a monoclonal anti-human PD-L1 antibody, or a single-chain variable fragment (scFv), comprising V.sub.H having the amino acid of SEQ ID NO: 3 and V.sub.L having the amino acid of SEQ ID NO: 5. The present invention is also directed to a chimeric antigen receptor fusion protein comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) of the present invention, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain. The inventors have shown that the PD-L1 CAR-T cells of the present invention are more effective than Avelumab PD-L1 CAR-T cells in killing several cancer cell lines. PD-L1 CAR-T can be used alone or in combination with other agent in an immunotherapy.

The present disclosure relates to a novel platform for immunotherapy which combines CAR engineered γδ T cells with armoring interleukin IL-18 that can be expressed constitutively or inducibly, or with a chimeric cytokine receptor comprising the endodomain of the IL-18 receptor. The system/platform and the associated methods according to the present disclosure have advantages such as increased immune cell potency and persistence for therapeutic applications.

The present invention relates to a targeting module comprising a chemically synthesized peptide binding moiety specific for a human cell surface protein or protein complex, a kit comprising the targeting module and a vector or a cell comprising a nucleic acid encoding a universal chimeric antigen receptor and the use for the treatment of cancer, infections and autoimmune disorders.

Provided herein are methods and compositions useful for treating PDL1 and/or PDL2 positive cancers through adoptive cell transfer of T cells genetically engineered to express a PD1-specific chimeric antigen receptor. Co-stimulatory domains such as Dap 10 may be included to enhance efficacy.

The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.

The presently disclosed subject matter provides for methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to chimeric antigen receptors (CARs) that specifically target human mesothelin, and immunoresponsive cells comprising such CARs. The presently disclosed mesothelin-targeted CARs have enhanced immune-activating properties, including anti-tumor activity.

The present invention generally embraces the treatment of diseases by targeting cells expressing an antigen on the cell surface. In particular the invention relates to recombinant antigen receptors and uses thereof. T cells engineered to express such antigen receptors are useful in the treatment of diseases characterized by expression of one or more antigens bound by the antigen receptors.

The presently disclosed subject matter provides for methods and compositions for treating a neoplasia (e.g., multiple myeloma). It relates to chimeric antigen receptors (CARs) that specifically target Fc Receptor-like 5 (FcRL5), e.g., domain 9 of FcRL5, and immunoresponsive cells comprising such CARs. The presently disclosed FcRL5-targeted CARs have enhanced immune-activating properties, including anti-tumor activity.

The invention provides highly effective and versatile CRISPR/Cas protein variants, compositions, methods and uses thereof in gene editing. More specifically, the invention relates to PAM-reduced or PAM-abolished Cas proteins and chimeras, complexes and conjugates thereof, genetic editing systems and to therapeutic and non-therapeutic methods and uses of the PAM-reduced or PAM-abolished Cas proteins.

Chimeric antigen receptors (CARs) with binding domains derived from a novel suite of human CD33-binding antibodies are described. The CARs include optimized short and intermediate spacer regions. The current disclosure also provides methods of cell expansion/activation processes utilizing IL-2, IL-7, IL-15, and/or IL-21 that improve cellular proliferation and cell lysis of the CARs as described.