The present disclosure pertains to methods of modifying an immune cell by delivering a modified messenger RNA (mRNA) encoding a chimeric antigen receptor (CAR) and modified immune cells comprising CARs.

The present disclosure provides a dendric cell tumor vaccine comprising a chimeric antigen receptor for activating the dendritic cell and a tumor antigen. The present disclosure also provides compositions and methods of making the dendritic cell tumor vaccine, and the methods of using the dendritic cell tumor vaccine to treat cancer.

Embodiments of the present disclosure relate to compositions and methods of enhancing lymphocytes' ability to treat cancer patients. Embodiments relate to a polynucleotide comprising a nucleic acid encoding a chimeric antigen receptor (CAR), a nucleic acid encoding an Oxygen-Dependent Degradation domain (ODD), and a nucleic acid encoding one or multiple sequences of Hypoxia-Response Element (HRE).

An exemplary combination drug includes (a1) an immunoresponsive cell expressing interleukine-7, CCL19, and a cell surface molecule that specifically recognizes a cancer antigen or (a2) one or more kinds of cells, one or more kinds of nucleic acid delivery vehicles, or a combination thereof, which cooperatively include a nucleic acid encoding interleukine-7 and a nucleic acid encoding CCL19; and (b) an immunosuppression inhibitor, and the drug is for use in treatment of a cancer in a subject. An exemplary immunoresponsive cell expresses interleukin-7, CCL19, an immunosuppression inhibiting polypeptide, and a cell surface molecule that specifically recognizes a cancer antigen.

An exemplary combination drug includes (a1) an immunoresponsive cell expressing interleukine-7, CCL19, and a cell surface molecule that specifically recognizes a cancer antigen or (a2) one or more kinds of cells, one or more kinds of nucleic acid delivery vehicles, or a combination thereof, which cooperatively include a nucleic acid encoding interleukine-7 and a nucleic acid encoding CCL19; and (b) an immunosuppression inhibitor, and the drug is for use in treatment of a cancer in a subject. An exemplary immunoresponsive cell expresses interleukin-7, CCL19, an immunosuppression inhibiting polypeptide, and a cell surface molecule that specifically recognizes a cancer antigen.

The invention provides Natural Killer (NK) cells that have a reduced or ablated Signal Regulatory Protein Alpha (SIRPα-) function when compared to a NK cell having an unmodified SIRPα-function that effectively kills a population of cancer cells that express CD47.

Provided is an anti-mesothelin chimeric antigen receptor specifically binding to mesothelin. The anti-mesothelin chimeric antigen receptor according to an aspect exhibits an ability to specifically bind to mesothelin, and thus may be usefully applied to preventing or treating mesothelin-overexpressing cancers.

Anti-BCMA antibodies and chimeric antigen receptors (CARs) are provided. Immune cells expressing the anti-BCMA CAR can be used to treat cancer. The anti-BCMA antibodies and CARs can recognize the extracellular domains of human BCMA. The anti-BCMA CAR T cells show specific cytotoxicity towards BCMA-positive target cells.

The present disclosure provides modified immune cells or precursors thereof (e.g. T cells) comprising a chimeric antigen receptor (CAR) capable of binding human PSCA. CARs capable of binding human PSCA, and nucleic acids encoding the same are also provided. Provided herein are bispecific CARs capable of binding human PSCA and human PSMA, nucleic acids encoding the same, and modified immune cells comprising the same. Modified immune cells comprising a PSMA CAR and a PSCA CAR are also provided. Compositions and methods of treatment are also provided.

The present invention provides a use of IFN-γ in preparing an anti-tumor adjuvant drug, wherein the IFN-γ enhances killing effect of the T cell preparation on tumor cell by sensitizing the tumor cell; the T cell preparation comprises non-genetically engineered T cell and/or genetically engineered T cell; and the IFN-γ comprises full-length or fragment of wild-type or mutant IFN-γ. The present invention revises the current understanding of IFN-γ in the prior art and finds that the IFN-γ inhibits the acquired immune resistance mediated by PD-L1-PD-1 and enhances the anti-tumor effect of immunotherapy by activating the IFN-γ signaling pathway in tumor cell.