Described herein are methods and compositions for treating a disease, e.g. cancer (including solid tumors) inflammatory disease, autoimmune disease, or fibrosis. Method for treating a disease in a subject, the method including administering to the subject a composition containing an oncolytic virus and an immune cell, wherein the immune cell is infected with an oncolytic virus.

Provided are genetically engineered induced pluripotent stem cells (iPSCs) and derivative cells thereof expressing mono- and/or bi-specific chimeric antigen receptors (CAR) with anti-CD133 and anti-EGFR antigen binding domains, and methods of using the same. Also provided are compositions, polypeptides, vectors, and methods of manufacturing.

The present invention relates to humanized antibodies or antigen-binding fragments capable of binding specifically to mesothelin antigen and various uses thereof.

Provided herein are a recombinant chimeric antigen receptor (CAR) fusion protein, a method of modifying an immune cell into a CAR immune cell by treating the immune cell with the recombinant CAR fusion protein, and a method of treating cancer by administering the CAR immune cell to a subject in need thereof.

Provided herein, inter alia, are methods for expanding a population of human group 2 innate lymphoid cells (ILC2), and methods of treating cancer in a subject including administering to the subject the population of expanded human ILC2. Further provided are genetically engineered human ILC2s including chimeric antigen receptors, and methods of treating cancer in a subject including administering to the subject the genetically engineered human ILC2.

Multispecific proteins that bind and specifically redirect NK cells to lyse a target cell of interest are provided without non-specific activation of NK cells in absence of target cells. The proteins have utility in the treatment of disease, notably cancer or infectious disease.

Compositions and methods for eradicating tumor cells using novel compositions are contemplated. In one aspect, a pharmaceutical composition comprising a CAR scaffold and an antigen binding domain in a single chimeric species is provided. In some aspects, the CAR scaffold may comprise a CD28 costimulatory signaling region and a CD3 activation domain or a complete CD3 activation domain. In some aspects, the CAR scaffold may be codon-optimized for improved expression in mammalian cell lines and/or for improved function upon transfection into natural killer (NK) or other immune cells. In further aspects, the antigen binding domain may comprise a VL and VH domain linked by a spacer and may be codon optimized. A CD64 leader sequence may be attached to the antigen binding domain, e.g., at the N-terminus of the antigen binding domain.

The invention relates to novel chimeric antigen (CAR) mRNA molecules, the methods of generating the molecules and methods of treating cancer with the molecules.

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.

This application relates to methods for overcoming or preventing resistance of a KRAS mutant cancer cell to a growth inhibition and/or cell death induction by a KRAS inhibitor or a SHP2 inhibitor, as well as to methods for enhancing sensitivity of a KRAS mutant cancer cell to a KRAS inhibitor or a SHP2 inhibitor. The application further relates to methods of treating a KRAS mutant cancer in a subject, the method comprising administering to the subject an effective amount of a KRAS inhibitor or a SHP2 inhibitor and an inhibitor of expression or function or a degrader or a binding partner of one or more of various proteins described herein. Related pharmaceutical compositions and kits are also disclosed.