Provided are B cell-activating factor receptor (BAFF-R)-binding molecules, in particular, to human antibodies specific for BAFF-R, including antibody fragments. The present disclosure further relates to recombinant receptors, including chimeric antigen receptors (CARs) that contain such antibodies or fragments, and polynucleotides that encode the antibodies, antigen-binding fragments or receptors specific for BAFF-R. Also provided are CARs which contain extracellular binding domains that bind to BAFF-R and B-lymphocyte antigen CD19 (CD19), genetically engineered cells expressing such CARs, and uses thereof in adoptive cell therapy.

MAGE-A4, or Melanoma-Associated Antigen A4, is a cancer-testis antigen (CTA) on the X chromosome. The present disclosure provides MAGE-A4-specific chimeric antigen receptors, cells expressing such chimeric antigen receptors, and MAGE-A4 specific isolated antibodies. In certain embodiments, engineered cells expressing the chimeric antigen receptors of the present disclosure are capable of inhibiting the growth of tumors expressing MAGE-A4. The engineered cells of the present disclosure are useful for the treatment of diseases and disorders in which an upregulated or induced MAGE-A4-targeted immune response is desired and/or therapeutically beneficial. For example, engineered cells expressing the MAGE-A4-specific chimeric antigen receptors of the present disclosure are useful for the treatment of various cancers.

The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.

An immunoresponsive cell, such as a T-cell expressing (i) a second generation chimeric antigen receptor comprising: (a) a signalling region; (b) a co-stimulatory signalling region; (c) a transmembrane domain; and (d) a binding element that specifically interacts with a first epitope on a target antigen; and (ii) a chimeric costimulatory receptor comprising (e) a co-stimulatory signalling region which is different to that of (b); (f) a transmembrane domain; and (g) a binding element that specifically interacts with a second epitope on a target antigen.

This arrangement is referred to as parallel chimeric activating receptors (pCAR). Cells of this type are useful in therapy, and kits and methods for using them as well as methods for preparing them are described and claimed.

The present invention relates to a multi-span chimeric antigen receptor (CAR) which comprises: i) at least one extra-cellular antigen binding domain; ii) a plurality of linked transmembrane domains; and iii) at least one intracellular signalling domain.

Provided herein are acute myeloid leukemia antigen targets for chimeric receptors and methods of using same.

Provided herein are chimeric antigen receptors that binds specifically to B-cell maturation antigen (BCMA) and CD307e, nucleic acids that encode these chimeric antigen receptors, and methods of making and using these chimeric antigen receptors.

A CD19-OR-CD20 chimeric antigen receptor (CAR) protein construct is provided. Also provided are nucleic acids encoding the CD19-OR-CD20 CAR; and methods of use, e.g. in the treatment of B cell malignancies. The CD19-OR-CD20 CAR of the invention is a bispecific CAR that can trigger T-cell activation upon detection of either CD19 or CD20 (or both). It is a single molecule that confers two-input recognition capability upon human T cells engineered to stably express this CAR.

Embodiments of the disclosure encompass methods and compositions that enhance adoptive cell therapy by preventing or at least reducing on-target off-tumor effects of adoptive cell therapy. The disclosure concerns an immune effector cells of any type that are engineered to express two separate chimeric molecules: an activating chimeric antigen receptor that activates the immune effector cell through costimulatory domains following binding to a first antigen, and an inhibitory chimeric antigen receptor that inhibits cell-mediated activation upon binding to a second antigen. In specific cases, the inhibitory chimeric antigen receptor prevents fratricide and exhaustion by inhibiting activation of the cell through the activating chimeric antigen receptor when the inhibitory chimeric antigen receptor binds a particular antigen, including one adopted by sibling engineered immune effector cells through trogocytosis.

A CD19-OR-CD20 chimeric antigen receptor (CAR) protein construct is provided. Also provided are nucleic acids encoding the CD19-OR-CD20 CAR; and methods of use, e.g. in the treatment of B cell malignancies. The CD19-OR-CD20 CAR of the invention is a bispecific CAR that can trigger T-cell activation upon detection of either CD19 or CD20 (or both). It is a single molecule that confers two-input recognition capability upon human T cells engineered to stably express this CAR.