Provided herein are chimeric antigen receptors (CARs), such as those specific for BCMA, that have improved properties, including increased CAR T cell binding to BCMA and improved CAR T cell killing of BCMA-expressing cancer cells. Use of the CARs in immune cells (e.g., T cells), compositions (e.g., CARs and nucleic acid constructs encoding the same), and methods are also contemplated.

Aspects of the disclosure relate to chimeric antigen receptors (CARs) comprising an antigen binding domain (e.g., anti-TSHR), transmembrane domain (e.g., CD28), and a cytoplasmic domain (e.g., CD27, CD-137, etc.) and a safety mechanism comprising an inducible apoptosis trigger. In some aspects, the disclosure relates to use of the CARs in T cells, compositions, kits and methods for the treatment of thyroid cancers.

The present invention provides a chimeric antigen receptor (CAR) comprising; (i) a B cell maturation antigen (BCMA)-binding domain which comprises at least part of a proliferation-inducing ligand (APRIL); (ii) a spacer domain (iii) a transmembrane domain; and (iv) an intracellular T cell signaling domain. The invention also provides the use of such a T-cell expressing such a CAR in the treatment of plasma-cell mediated diseases, such as multiple myeloma.

The present disclosure includes compositions and methods for treating gastrointestinal inflammatory disease and/or cancers. In certain aspects, the disclosure includes an isolated cell comprising a nucleic acid vector comprising a gene encoding the transcription factor ZBTB20 which is operably linked to a promoter.

Embodiments relate to novel compositions and methods for treating solid tumors. Other embodiments relate to generating T cells able to home to and treat solid tumors. In accordance with these embodiments, T-cells expressing at least one C-X-C Motif Chemokine Receptor (CXCR) and chimeric antigen receptors (CARs) able to bind to B7H3 are disclosed. In certain embodiments, the present disclosure provides for polynucleotides and vectors encoding a CAR and a CXCR together or in separate constructs, where the CAR binds to B7H3 in solid tumor cells, other tumors, or malignancies. In other embodiments, methods of making T cells expressing a CAR that binds to B7H3 and expressing one or more CXCR are provided. In some embodiments, methods of preventing, treating, or ameliorating tumors or malignancies in a subject are disclosed including administering a composition of T cells expressing at least one CXCR and CARs that bind to B7H3.

The present invention relates to therapeutic and prophylactic methods based on inhibition of CIS in NK cells. In particular, the present invention relates to treating or preventing a NK-responsive condition by administering to a subject a CIS inhibitor, or administering CIS-inhibited NK cells. The invention further relates to methods for identifying a CIS inhibitor, and for determining a likelihood of cancer response to treatment with CIS inhibition.

Disclosed herein are cells that are immune cells or precursor cells thereof, which cells recombinantly express a chimeric antigen receptor (CAR), and a dominant negative form of an inhibitor of a cell-mediated immune response of the immune cell, wherein the CAR binds to a cancer antigen. Also disclosed herein are T cells that recognize and are sensitized to a cancer antigen, which T cells recombinantly express a dominant negative form of an inhibitor of a T cell-mediated immune response. Additionally provided are methods of using such cells to treat cancer in a subject in need thereof.

Disclosed herein are methods and compositions for cell-based immunotherapies that simultaneously target the tumor microenvironment (TME) via NKG2D ligands and tumor cells via tumor-associated antigens, specifically using immune effector cells as the platform due to their reduced toxicity against normal tissue. In some embodiments, immune effector cells co-express an NKG2D cytotoxic CAR and a CAR directed against a tumor-associated antigen that provides costimulatory signals to the immune effector cell, thus killing only in the presence of both antigens specifically within the TME. In contrast, within normal tissue that might express the tumor-associated antigen, but where self-HLA is also expressed, the costimulatory signal by itself is insufficient for immune effector cell activation, thereby preventing off-tumor toxicity.

Provided herein are chimeric antigen receptors (CARs), such as those specific for BCMA, that have improved properties, including increased CAR T cell binding to BCMA and improved CAR T cell killing of BCMA-expressing cancer cells. Use of the CARs in immune cells (e.g., T cells), compositions (e.g., CARs and nucleic acid constructs encoding the same), and methods are also contemplated.

The present invention relates to chimeric antibody receptors with anti-cotinine antibodies linked, and use thereof. A T cell presenting the chimeric antibody receptor on the surface secretes interferon gamma specifically for a target molecule of a cotinine-conjugated binding molecule that is added together therewith and induces cell death of the cell expressing the target molecule by the T cell. On the contrary, by administering a cytotoxic agent conjugated with cotinine, cell death of the chimeric antigen receptor T cell is induced. Therefore, if necessary, a cytotoxic agent conjugated with cotinine can be administered to remove the chimeric antigen receptor T cells that have been already administered, thereby suppressing immune side effects due to hyperactivity of T cells. Thus, the chimeric antigen receptor to which the anti-cotinine antibody is linked can be effectively and safely used for the treatment of cancer.