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

Summary
Chimeric Antigen Receptor T cell (CAR-T) therapies that specifically target B-cell maturation antigen (BCMA) are strong therapeutic candidates for patients with plasma cell malignancy diseases such as, multiple myeloma (MM), as well as for patients with Hodgkin’s lymphoma. BCMA is a cell surface protein preferentially expressed on a subset of B cells and mature plasma cells, but not on other cells in the body. The limited expression of BCMA on B and plasma cells makes BCMA an attractive therapeutic target for B cell and plasma cell malignancy diseases. The 12 anti-BCMA CARs described are fully human CARS and have the potential to treat patients with various plasma cell and B cell malignancy diseases.
NIH Reference Number
E-183-2017
Product Type
Keywords
  • Multiple Myeloma, MM, Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Hodgkin’s Lymphoma, Non-Hodgkin’s Lymphoma, B-cell Maturation Antigen, BCMA, Adoptive Cell Therapy, ACT, Chimeric Antigen Receptor, CAR, Plasma Cell Malignancies, B-cell Malignancies
  • Cancer, Biologic, Kochenderfer
Collaboration Opportunity
This invention is available for licensing and co-development.
Contact
Description of Technology

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
  • 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 
Competitive Advantages
  • 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 
Inventor(s)

Jim Kochenderfer M.D. (NCI), Norris Lio Lam (NCI), Benjamin Buelow (UCSF)

Development Stage
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]

Patent Status
  • U.S. Provisional: U.S. Provisional Patent Application Number 62/527,556 , Filed 30 Jun 2017
Related Technologies
  • E-040-2012
Therapeutic Area
Posted
Tuesday, March 13, 2018