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.
- Treatment of plasma cell malignancy diseases such as multiple myeloma
- Treatment of B cell malignancy diseases such as Hodgkin’s lymphoma and non-Hodgkin’s lymphoma
- The fully human nature of this anti-BCMA CAR can increase therapeutic effectiveness because it is less immunogenic to human patients
- The fully human CARs are already known to bind to BCMA in vitro and in vivo
Jim Kochenderfer M.D. (NCI), Norris Lio Lam (NCI), Benjamin Buelow (UCSF)
Ali S.A, et al. T cells expressing an anti–B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma. [PMID 27412889]
- U.S. Provisional: U.S. Provisional Patent Application Number 62/527,556 , Filed 30 Jun 2017