D domain (DD) containing polypeptides (DDpp) that specifically bind targets of interest (e.g., BCMA, CD123, CS1, HER2, AFP, and AFP p26) are provided, as are nucleic acids encoding the DDpp, vectors containing the nucleic acids and host cells containing the nucleic acids and vectors. DDpp such as DDpp fusion proteins, are also provided as are methods of making and using the DDpp. Such uses include, but are not limited to diagnostic and therapeutic applications.

Provided is an engineered T cell. The expression level of an HLA class I molecule on the surface of the T cell is down-regulated to 10-50% of that of a non-engineered T cell. The expression of the T cell down-regulates a functional protein of the HLA class I molecule. The functional protein down-regulates at least one of HLA-A, HLA-B, and HLA-E molecules of the HLA class I molecule. The T cell may be an allogeneic CAR-T cell. Also provided is an application of the T cell or the allogeneic CAR-T cell.

Provided are a chimeric antigen receptor targeting CD20 antigen and a preparation method thereof. The extracellular antigen binding domain of the chimeric antigen receptor includes an antibody heavy chain variable region shown in SEQ ID NO: 7 or 9 or 33 and an antibody light chain variable region shown in SEQ ID NO: 11 or 13 or 35, and is capable of killing tumor cells.

Provided herein are CAR-T compositions that are directed to GPC3, including a chimeric receptor, and engineered immune cells to GPC3. The disclosure also provides vectors, compositions, and methods of treatment using GPC3 antigen binding molecules and engineered immune cells, optionally in combination with expression of IL-18. GPC3 CAR compositions provided herein can be used for the treatment of certain cancers.

A population of immune cells comprising modified immune cells co-expressing a chimeric antigen receptor comprising, inter alia, an IB-2Kβ cytoplasmic signaling domain. Also provided herein are genetically engineered immune cells having reduced production of interferon gamma (IFNy). Such genetically engineered immune cells may have a disrupted endogenous IFNy gene, a disrupted endogenous IFNy receptor (IFNyR) gene, or both. Alternatively, the immune cells may express an IFNy antagonist.

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.

Provided are a genetically modified immunocyte expressing a chimeric antigen receptor (CAR) comprising an antigen binding domain specifically binding to cancer cells and/or expressing TRAIL, a composition for preventing or treating cancer, the composition comprising the immunocytes, a cell therapeutic agent, a method of providing information for cancer diagnosis, and a method of preparing the genetically modified immunocyte.

The present invention relates to regulatory nucleic acid sequences, in particular CNS—specific promoters, and elements thereof. The invention also relates to expression constructs, vectors, virions, pharmaceutical compositions and cells comprising such promoters and to methods of their use. The regulatory nucleic acid sequences are of particular utility for gene therapy applications.

The present disclosure provides systems for inducing activity of immune cells and methods of immunotherapy. Systems of the present disclosure for inducing immune cell activity comprise a chimeric antigen receptor, a T cell receptor, and various combinations thereof.

The invention relates to chimeric antigen receptors (CARs) targeting a cancer-associated antigen and their use for treatment of a tumor or cancer. In particular, the invention provides compositions and methods for treating diseases associated with the antigen NGcGM3. The invention also relates to CARs specific to NGcGM3, 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 NGcGM3.