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.



Potential Commercial Applications: Competitive Advantages:
  • 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 


Development Stage:
Pre-clinical (in vivo)

Related Invention(s):
E-040-2012


Inventors:

Jim Kochenderfer (NCI)  ➽ more inventions...

Norris Lio Lam (NCI)  ➽ more inventions...

Benjamin Buelow (UCSF)  ➽ more inventions...


Intellectual Property:
Application No. 62/527,556

Publications:
Ali S.A, et al. T cells expressing an anti–B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma.  PMID 27412889

Collaboration Opportunity:

Licensing and research collaboration


Licensing Contact:
John Hewes, Ph.D.
Email: John.Hewes@nih.gov
Phone: 240-276-5515

OTT Reference No: E-183-2017
Updated: Mar 13, 2018