The present application provides a MSLN-containing chimeric antigen receptor, iNKT cells transduced by the chimeric antigen receptor and use of the chimeric antigen receptor and the INKT cells in treatment of liver cancer, particularly cholangiocarcinoma. The present application utilizes the characteristic that iNKT cells can home and colonize the liver, and selects a proper MSLN antibody sequence, thereby realizing high tumor killing efficiency and CAR-iNKT cell proliferation speed; the Anti-MSLN CAR-INKT cell can effectively infiltrate into the liver tumor part, greatly improve the curative effect, reduce the recurrence and alleviate the toxic and side effects.

The present invention relates to agents, compositions, and methods to confer and/or increase immune responses mediated by cellular immunotherapy.

Provided herein, inter alia, are compositions and methods including T-cell cultures enriched for gdT cells, the gdT cells expressing a CAR, and related methods for generating said cells. In an aspect provided herein is a method for generating a T-cell culture enriched for gamma delta T-cells (gd T-cells or T cells). In another aspect, a method for generating a gdT-cell expressing a Chimeric Antigen Receptor (CAR) is provided. The method includes introducing a nuclei acid encoding a CAR to a gdT-cell obtained as provided herein, including embodiments thereof.

The invention provides compositions and methods for treating diseases associated with expression of EGFRvIII. The invention also relates to chimeric antigen receptor (CAR) specific to EGFRvIII, vectors encoding the same, and recombinant T cells comprising the anti-EGFRvIII CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an anti-EGFRvIII binding domain.

The present disclosure is directed to antigen-binding molecules that specifically bind peptide fragments of tumor antigens, wherein the peptide fragment is capable of being presented by more than one type of major histocompatibility complex (MHC) class II molecule. In some aspects, the tumor antigen is a WT1 polypeptide. Other aspects are directed to antibodies, multispecific antibodies, and chimeric antigen receptors, and nucleotides encoding the same. Other aspects are directed to methods of administering the same to a subject in need thereof.

Single domain antibodies which specifically bind to mesothelin and mesothelin binding proteins, anti-mesothelin anti-bodies and antibody fragments thereof, antibody drug conjugates, synthetic immune receptors, and diagnostic agents comprising the same are disclosed. Also disclosed are pharmaceutical compositions comprising any of the foregoing and uses of any of the foregoing in the treatment and/or diagnosis and/or monitoring of a disease associated with mesothelin expression.

This invention is directed in one main aspect to a cell composition comprising a population of engineered mucosal-associated invariant T (MAIT) cells derived from placental tissue expressing an exogenous chimeric antigen receptor (CAR). The invention further discloses a unique placental MAIT cell population, cell compositions comprising the MAIT cell population, and methods of use.

This invention is directed in one main aspect to a cell composition comprising a population of engineered mucosal-associated invariant T (MAIT) cells derived from placental tissue expressing an exogenous chimeric antigen receptor (CAR). The invention further discloses a unique placental MAIT cell population, cell compositions comprising the MAIT cell population, and methods of use.

The invention provides compositions and methods for treating diseases associated with expression of a cancer associated antigen as described herein. The invention also relates to chimeric antigen receptor (CAR) specific to a cancer associated antigen as described herein, vectors encoding the same, and recombinant T cells comprising the CARs of the present invention. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an antigen binding domain that binds to a cancer associated antigen as described herein.

Binding proteins specific for Msln20-28 or Msln530-538 peptides are provided herein. Polynucleotides encoding the binding proteins, as well as compositions and recombinant host cells comprising the binding proteins or polynucleotides are also provided. The compositions and recombinant host cells may be used to treat a subject having mesothelioma, pancreatic cancer, ovarian cancer, lung cancer, a cancer wherein an Msln20-28 peptide is expressed on a tumor cell of the cancer, or a cancer wherein an Msln530-538 peptide is expressed on a tumor cell of the cancer.