Fully-human Heavy-chain-only Anti-B-cell Maturation Antigen (BCMA) Chimeric Antigen Receptors (CARs)

Immortalization of plasma cells leads to plasma cell malignancy diseases such as multiple myeloma (MM). B-cell maturation antigen (BCMA) is a protein that is preferentially expressed by malignant and normal B cells and plasma cells, butnot on other cells in the body. This limited expression profile suggests that BCMA is a promising target for anticancer therapeutics for cancers in which there is excess production of plasma cells and B cells. 
Researchers in the National Cancer Institute (NCI) Experimental Transplantation and Immunology Branch (ETIB) previously reported anti-BCMA CARs, which are currently being tested in the clinic for patients with multiple myeloma. While the results from clinical trials have demonstrated the efficacy of anti-BCMA CARs, the CAR being used in this clinical trial has an antigen recognition domain derived from mouse antibody; this allows 
for the possibility of an immune response by the patient against the CAR. The development of CARs with antigen-recognition domains comprising a fully human heavy chain variable region can mitigate this potential immunogenicity against the CAR T cells, thereby enhancing therapeutic function.  
The inventors have developed 12 novel anti-BCMA CARs with fully human heavy chain variable region sequences, each of which specifically recognizes BCMA in vitro and in vivo. Each of these CARs is available for licensing under a variety of conditions, including expression on autologous or allogeneic T cells.