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

Description:

Abstract:

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.

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 

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 
Patent Information:
For Information, Contact:
David Lambertson
Senior Technology Transfer Manager
NIH Technology Transfer
240-276-6467
david.lambertson@nih.gov
Inventors:
James Kochenderfer
Norris Lam
Benjamin Buelow
Keywords:
act
adoptive cell therapy
B-cell Malignancies
B-cell Maturation Antigen
BCMA
BIOLOGIC
CANCER
CAR
chimeric antigen receptor
Hodgkin Lymphoma
Hodgkin’s Lymphoma
Kochenderfer
Mm
MULTIPLE MYELOMA
Non-Hodgkin Lymphoma
Non-Hodgkin’s Lymphoma
Plasma Cell Malignancies
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