Provided are antibodies, fragments thereof, chimeric antigen receptors (CARs) and T cell receptors (TCRs) comprising one or more of the dual TACI-BCMA binding domains disclosed herein. Provided are compositions, cells and cell therapies comprising the same. Further provided are methods of treatment.

Materials and methods for producing genome-edited cells engineered to express a chimeric antigen receptor (CAR) construct on the cell surface, and materials and methods for genome editing to modulate the expression, function, or activity of one or more immuno-oncology related genes in a cell, and materials and methods for treating a patient using the genome-edited engineered cells.

In one embodiment, the present disclosure provides an engineered cell having a first chimeric antigen receptor polypeptide including a first antigen recognition domain, a first signal peptide, a first hinge region, a first transmembrane domain, a first co-stimulatory domain, and a first signaling domain; and a second chimeric antigen receptor polypeptide including a second antigen recognition domain, a second signal peptide, a second hinge region, a second transmembrane domain, a second co-stimulatory domain, and a second signaling domain; wherein the first antigen recognition domain is different than the second antigen recognition domain.

Provided are a CAR-T cell specifically recognizing CD70, and a preparation method therefor. The method comprises expressing a SCFV(Anti CD70)-CD8-4-1BB-CD3ζ molecule in a T cell. The CAR-T cell has tumor killing activity and may be used for preparing a medication in the treatment of a tumor with the high expression level of CD70 molecules.

A modified T cell comprising a functional exogenous receptor is provided. The functional exogenous receptor comprises: (a) an extracellular ligand binding domain, (b) a transmembrane domain, and (c) an intracellular signaling domain (ISD) comprising a chimeric signaling domain (CMSD), wherein the CMSD comprises a plurality of Immune-receptor Tyrosine-based Activation Motifs (ITAMs) optionally connected by one or more linkers. Further provided are vectors, methods of producing, pharmaceutical compositions, kits, and methods of treatment thereof.

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.

Methods are disclosed for inhibiting the development of a tumor in a subject. The methods include administering to a subject a therapeutically effective amount of a dominant negative tumor necrosis factor (DN-TNF)-α protein and/or a nucleic acid encoding the DN-TNF-α protein. The DN-TNF-α protein and/or a nucleic acid encoding the DN-TNF-α protein can be administered alone or in combination with other agents.

The present disclosure provides methods of treating cancer or light chain amyloidosis in a subject in need thereof comprising administering a combination therapy comprising an effective amount of Form A of nirogacestat dihydrobromide and a B-cell maturation antigen (BCMA)-directed therapy to the subject and the uses thereof.

The present disclosure provides methods of treating cancer or light chain amyloidosis in a subject in need thereof comprising administering a combination therapy comprising an effective amount of Form A of nirogacestat dihydrobromide and a B-cell maturation antigen (BCMA)-directed therapy to the subject and the uses thereof.

The invention relates to a chimeric antigen receptor (CAR) suitable for the treatment of human subjects, comprising: (i) a signalling chain comprising a transmembrane domain and a signalling domain; (ii) a non-signalling chain comprising a target binding domain and a transmembrane domain;

wherein, one of said chains further comprises a HIV Integrase catalytic core domain (CCD) or a functional fragment or variant thereof, and the other chain further comprises a LEDGF/p75 integrase binding domain (IBD), or a functional fragment or variant thereof.