The invention relates to a composition and related methods for reducing tumor volume and/or increasing the survival of a cancer patient. The composition comprises a recombinant MVA encoding a Tumor Associated Antigen (“TAA”) as well as 4-1BBL and/or CD40L and can be administered to a subject in any suitable manner, including by intravenous and/or intratumoral administration.

Chimeric antigen receptors (CARs) which include an antigen binding protein that binds to a discontinuous epitope on human claudin-3 comprising at least N38 and E153 of SEQ ID NO:13 are described. Also described herein includes polynucleotides encoding the antigen binding protein, the CARs, immune effector cells containing the CARs, pharmaceutical compositions containing the immune effector cells, and methods of treating cancer with the immune effector cells.

Provided are genetically modified NK cells expressing a chimeric antigen receptor targeting an BCMA superfamily receptor. The CAR can comprise an intracellular domain of FcεRIγ and further recombinant proteins expressed by the genetically modified NK cells are CD16, autocrine growth stimulating cytokines, and optionally one of IL-12, a TGF-beta trap, or a homing receptor. Also described are methods for treating a patient having or suspected of having a disease that is treatable with NK-92 cells, such as cancer, comprising administering to the patient the genetically modified NK cells.

The invention provides compositions and methods for treating diseases associated with expression of a cancer associated antigen as described herein. The invention also relates to chimeric antigen receptor (CAR) specific to a cancer associated antigen as described herein, 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 a cancer associated antigen as described herein.

An embodiment relates to an anti-BCMA-binding protein and, more specifically, provides an isolated BCMA-binding protein comprising an antigen-binding domain that binds specifically to BCMA, wherein the antigen-binding domain comprises: i) heavy chain variable domain complementarity determining region 1 (VH-CDR1) comprising the amino acid sequence of SEQ ID NO: 1 or an amino acid sequence having at least 80% homology to SEQ ID NO: 1; ii) VH-CDR2 comprising the amino acid sequence of SEQ ID NO: 2 or an amino acid sequence having at least 80% homology to SEQ ID NO: 2; and iii) VH-CDR3 comprising the amino acid sequence of SEQ ID NO: 3 or an amino acid sequence having at least 80% homology to SEQ ID NO: 3.

The present invention provides a chimeric antigen receptor (CAR) which binds a low density target antigen, which comprises a Fab antigen binding domain. The invention also relates to cells expressing such a CAR and their use in the treatment of disease.

The presently disclosed subject matter provides combination therapies for treating diseases or disorders, e.g., cancers. In particular, the present disclosure provides methods of treatment comprising administering genetically engineered cells and radiation.

The presently disclosed subject matter provides combination therapies for treating diseases or disorders, e.g., cancers. In particular, the present disclosure provides methods of treatment comprising administering genetically engineered cells and radiation.

The present disclosure provides compositions and methods for boosting, augmenting or enhancing the efficacy of the adoptive cellular immunotherapy by using modified T cells expressing an antigen binding protein in conjunction with modified cells (such as hematopoietic progenitor cells, modified human immune system cells or a combination thereof) expressing the antigen specifically bound by the antigen binding protein of the modified T cells.

The invention relates to a method of controlling the level of a polypeptide sequence comprising administering a polypeptide sequence fused to a ubiquitin targeting protein which comprises a minimal degron structural motif. In particular, the polypeptide sequence comprises a chimeric antigen receptor therefore the present invention is useful in methods of cell and gene therapy where the activity of the chimeric antigen receptor needs to be controlled.