Methods and compositions are provided related to therapeutic receptors, including chimeric antigen receptors (CARs), capable of specifically binding TYRP-1. The disclosed compositions include, for example, cells (e.g., immune cells) expressing TYRP-1 specific CARs, nucleic acids encoding TYRP-1 specific CARs, and TYRP-1 specific CAR polypeptides. Certain aspects relate to methods of treating cancer, including melanoma, using compositions comprising TYRP-1 specific CARs, for example cells expressing TYRP-1 specific CARs. In some embodiments, provided herein are chimeric polypeptides comprising a TYRP-1 binding domain, a hinge region, a transmembrane domain, and an intracellular signaling domain.

Provided is an antibody, which is capable of specifically binding to a B-cell maturation antigen (BCMA). The provided BCMA antibody is capable of specifically binding to an extracellular fragment of the BCMA and has excellent affinity and specificity; and the antibody is a functional antibody and has the activity blocking binding of the BCMA with its ligand APRIL. Immune cells constructed based on the antibody has an excellent specific killing function for a BCMA-positive tumor cell.

The present disclosure provides methods and compositions for genetically modifying lymphocytes, for example T cells and/or NK cells. In some embodiments, the methods include reaction mixtures, and resulting cell formulations, that are created using whole blood, or a component thereof that is not a PBMC, and additionally comprise T cells and recombinant retroviral particles having polynucleotides that encode a CAR. In some embodiments, modified lymphocytes are reintroduced into a subject subcutaneously. In some embodiments, polynucleotides that provide T cells the ability to regulate cell survival and proliferation in response to binding to a CAR, are provided.

Chimeric antigen receptors containing CD123 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

Provided herein are inhibitory chimeric antigen receptor compositions and cells comprising such compositions. Also provided are methods of using inhibitory chimeric antigen receptors and cells.

A humanized CD 19 antibody, and a chimeric antigen receptor thereof, an immune cell thereof and the use thereof are provided. The humanized CD19 antibody is based on a FMC63 chimeric antibody, which is subjected to humanization modification. A CAR-T and a dual CAR-T cell constructed based on the humanized antibody and the related use thereof are also provided. Compared with a CAR-T cell constructed by using FMC63, the CAR-T cell constructed based on the humanized antibody has higher killing effect and tumor removal ability.

A modified immune cell that has attenuated expression and/or activity of YTH N6-Methyladenosine RNA Binding Protein 2 (YTHDF2), and enhanced anti-tumor activity. A composition for stimulating T cell-mediated immune response to a cancer cell and/or a tumor antigen, including an agent capable of attenuating the expression and/or activity of YTHDF2, and a pharmaceutically acceptable excipient. A composition for treating cancer, comprising an agent capable of attenuating the expression and/or activity of YTHDF2. A method for activating an immune cell. A method for generating an immune cell. A method for treating a disease, disorder or condition associated with an expression of a tumor antigen in a subject in need thereof. A method for stimulating a T cell-mediated immune response to a cancer cell and/or a tumor antigen in a subject in need thereof.

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.

A vector comprising a first polynucleotide encoding a FOXP3 polypeptide and a second polynucleotide encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen recognition domain which specifically binds to a human leukocyte antigen (HLA), wherein the first polynucleotide and the second polynucleotide are operably linked to the same promoter, and wherein the first polynucleotide is upstream of the second polynucleotide.

Provided herein are compositions and methods for altering sensitivity of target cells to killing by γδ T cells.