Disclosed herein is a chimeric antigen receptor (CAR) comprising a single-chain variable fragment specific to Globo H, a hinge and transmembrane domain, a co-stimulatory molecule, and a cytoplasmic domain. According to some embodiments of the present disclosure, the CAR further comprises a single-chain variable fragment specific to PD-L1, and optionally, a fragment crystallizable region of an immunoglobulin. Also disclosed herein are isolated nucleic acids encoding the CAR pharmaceutical kits comprising the isolated immune cells expressing the CAR, and methods of treating cancers by using isolated immune cells.

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

Provided herein are Claudin 18.2 binding agents and chimeric antigen receptors (CARs) comprising a Claudin 18.2 binding molecule that specifically binds to Claudin 18.2; and immune cells comprising these Claudin 18.2-specific CARs, e.g., CAR-T cells. Also provided are methods of making and using Claudin 18.2-specific CARs and Claudin 18.2 binding agents, and immune cells comprising Claudin 18.2-specific CARs.

The present invention provides compositions and methods for inducing a CAR mediated trans-signal in a T cell. The trans-signaling CAR T cells comprise a first CAR having a first signaling module and a second CAR having a distinct second signaling module. The present invention also provides cells comprising a plurality of types of CARs, wherein the plurality of types of CARs participate in trans-signaling to induce T cell activation.

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.

Multi-specific antigen-binding constructs that target immunotherapeutics are described. The multi-specific antigen-binding constructs comprise a first antigen-binding polypeptide construct that binds to an immunotherapeutic (such as a CAR-T cell or a bispecific T-cell engager), and a second antigen binding polypeptide construct that binds to a tumour-associated antigen. Also described are methods of using the multi-specific antigen-binding constructs to re-direct or enhance the binding of the immunotherapeutic to a tumour cell, and methods of treating patients who have relapsed from or failed treatment with the immunotherapeutic.

Embodiments described herein relate to methods, devices, and computer systems thereof for the derivation of T CAR libraries (Universal Subject or Individual Subject) for personalized treatment of disease in a subject. In certain embodiments, differential screening of normal and diseased tissue expression data is utilized to determine disease-specific antigens and thereby generate T CAR cells reactive to such antigens to form a disease-specific library. In certain embodiments, determination of the most effective T CAR clones from the disease-specific library is based on the subject's own disease-specific antigens. In certain embodiments, a subject is treated with a therapeutically effective amount of T CAR clones.

Disclosed are chimeric antigen receptor (CAR) engineered T lymphocyte membrane coated nanoparticles (CAR-T MNP) compositions and methods of using the same for delivering therapeutics to a particular target.

Anti-PSMA antibodies (e.g., UniAbs?) and CAR-T structures are disclosed, along with methods of making such antibodies and CAR-T structures, compositions, including pharmaceutical compositions, comprising such antibodies and CAR-T structures, and their use to treat disorders that are characterized by the expression of PSMA.

An immunoresponsive cell, such as a T-cell expressing 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 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.