Provided herein are solid tumor antigen targets for chimeric receptors and chimeric inhibitory receptors, and methods of using the same, such as for the treatment of cancer.

A polypeptide comprising a chimeric antigen receptor (CAR) comprising (i) an extracellular domain capable of binding to a first antigen, (ii) a transmembrane domain, and (iii) an intracellular domain; and a domain capable of binding to a second antigen expressed on the surface of a cell that can interact with a T cell, wherein the CAR and the domain are fused by a peptide linker.

Provided herein are targeted cytokine constructs and method of engineered cell therapy by administering a targeted cytokine construct in combination with an engineered cell therapy, for use in treating a disease, e.g., a proliferative disease, e.g., a cancer.

Disclosed herein is a polynucleotide comprising a human codon-optimized sequence encoding a polypeptide comprising EGFR806CAR. The codon-optimized sequence may be incorporated into a construct comprising an optimal-functioning promoter, spacer, intracellular signaling domain, transmembrane domain, selection marker, at least one self-cleaving peptides, and EFGRt, in order to optimize expression. This sequence may then be expressed in cells, such as T cells, for the treatment or inhibition of a cancer, such as glioblastoma, liquid tumors, or solid tumors.

Provided herein are, inter alia, methods, compositions and kits for treating cancer, e.g., acute myeloid leukemia, including an engineered cell including various CAR constructs. Also included herein are kits for treating cancer, including engineered cells comprising various CAR constructs.

Provided are chimeric antigen receptors (CARs), which contain extracellular antigen-binding domains that bind to G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D) and B-cell maturation antigen (BCMA). The disclosure further relates to genetically engineered cells expressing such CARs, and uses thereof in adoptive cell therapy.

The present invention provides antibodies, as well as molecules having at least the antigen-binding portion of an antibody, recognizing a specific epitope of the protein CEACAM1 and optionally binds also other subtypes of the CEACAM protein family Disclosed antibodies and antibody fragments are characterized by specific CDR sequences. Methods of production and use in therapy and diagnosis, of such antibodies and antibody fragments are also provided.

Methods of producing T cells having reduced surface fucosylation and use thereof in adoptive cell therapy, in particular, in cancer treatment are provided.

The present invention provides, in certain aspects, a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15), and methods for producing such cells. The invention further provides methods of using a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15) to treat cancer in a subject or to enhance expansion and/or survival of NK cells.

The presently disclosed subject matter provides methods and compositions for treating cancer (e.g., melanoma). It relates to chimeric antigen receptors (CARs) that specifically target MDA (e.g., Trp1), and immunoresponsive cells comprising such CARs. The presently disclosed MDA-specific CARs have enhanced immune-activating properties, including anti-tumor activity.