HUMANIZED BCMA ANTIBODY AND BCMA-CAR-T CELLS

Smart overview of the Invention

The invention focuses on a humanized BCMA single-chain variable fragment (scFv) used in the creation of BCMA chimeric antigen receptor (CAR) fusion proteins. These proteins include an scFv, a transmembrane domain, co-stimulatory domains, and an activating domain. The BCMA-CAR-T cells developed from this technology exhibit specific cytotoxic activity against BCMA-positive tumor cells, particularly useful for treating multiple myeloma through adoptive immunity gene therapy.

Technical Background

Immunotherapy leverages T cells to target cancer cells by genetically modifying them with CAR constructs. CAR-T cells, designed to target tumor-associated antigens, offer a promising alternative to chemotherapy due to their ability to proliferate and persist in patients. CARs are composed of various domains, including monoclonal antibody-derived scFv, co-stimulatory domains like CD28 and 4-1BB, and an activation domain such as CD3-zeta.

BCMA Targeting

The B cell maturation antigen (BCMA) is a receptor overexpressed in multiple myeloma cells. Current therapies include monoclonal antibodies and CAR-T therapies targeting BCMA. The humanized BCMA protein consists of 184 amino acids with distinct extracellular, transmembrane, and cytoplasmic domains. This invention utilizes the strong binding affinity of a humanized BCMA antibody derived from a mouse monoclonal antibody to develop effective CAR-T cells against cancer.

Invention Details

The engineered humanized BCMA scFv comprises specific heavy and light chain sequences (SEQ ID NO: 3 and SEQ ID NO: 5). The CAR structure includes these scFv sequences, a transmembrane domain, co-stimulatory domains selected from options like CD28 or 4-1BB, and an activating CD3 zeta domain. The transmembrane domain can be derived naturally or artificially designed with hydrophobic residues.

Nucleic Acid Encoding and Application

A nucleic acid encoding the BCMA-CAR can be synthesized using conventional methods and inserted into vectors for cell introduction. Various virus vectors are applicable for this purpose, enhancing the delivery efficiency into host cells. Upon binding to a specific antigen via the CAR, the engineered T cell activates, leading to cytokine release and target cell destruction while stimulating other immune responses.