US20240182591
2024-06-06
Chemistry; metallurgy
C07K16/2878
A humanized BCMA single-chain variable fragment (scFv) has been developed, featuring specific amino acid sequences for both the heavy (VH) and light (VL) chains. The VH comprises the sequence of SEQ ID NO: 3, while the VL includes the sequence of SEQ ID NO: 5. This engineered antibody is designed to enhance targeting of BCMA-positive tumor cells, particularly in patients with multiple myeloma.
The invention includes a chimeric antigen receptor (CAR) fusion protein that integrates the humanized BCMA scFv along with several essential components. These components are a transmembrane domain, at least one co-stimulatory domain, and an activating domain. The resulting BCMA-CAR-T cells exhibit potent cytotoxic effects against tumors expressing the BCMA antigen.
Immunotherapy represents a cutting-edge strategy in cancer treatment, utilizing T cells to target and eliminate abnormal cells. By genetically modifying T cells with CAR constructs, these therapies enable targeted destruction of cancer cells while allowing T cells to proliferate within the patient’s body. This method stands out as an innovative alternative to traditional chemotherapy and antibody treatments.
The B cell maturation antigen (BCMA) is primarily expressed on mature B lymphocytes and is often overexpressed in multiple myeloma cases. Current therapeutic approaches targeting BCMA include various forms of monoclonal antibodies and CAR-T therapies. The engineered BCMA-CAR-T cells leverage this characteristic to specifically attack cancerous cells that overexpress this receptor.
The invention provides a method for creating a nucleic acid encoding the BCMA-CAR, which can be introduced into host cells using various viral vectors. Once activated by binding to specific antigens, CAR-T cells can release cytokines that not only destroy targeted tumor cells but also stimulate additional immune responses. This innovative approach aims to improve outcomes for patients suffering from multiple myeloma through enhanced adoptive immunity gene therapy.