Bivalent, Dual Specific Anti-CD22 Anti-CD19 Chimeric Antigen Receptors (CARs)


Chimeric antigen receptors (CARs) combine an antibody-based binding domain (and single chain fragment variable region, scFv) with T cell receptor signaling domains (CD3 zeta with a costimulatory domain, typically CD28 or 41BB). When T cells express CARs, they are activated in a major histocompatibility complex- (MHC) independent manner to kill tumor cells expressing the target to which the scFv binds.  CAR T cells targeting the B cell antigen CD19 have resulted in remissions in 60-80% of patients with pre-B cell precursor acute lymphoblastic leukemia (BCP-ALL). However, not all patients respond, and relapses occur in 10% or more of patients who receive anti-CD19 CAR therapy for acute lymphoblastic leukemia (ALL) - primarily due to the loss of the CD19 epitope. Thus, there is a need for advanced therapeutic options to treat those patients who either relapse or are non-responders.
  
To overcome these current limitations, the National Cancer Institute’s Pediatric Oncology Branch (NCI POB) developed an active CD19/CD22 targeted CAR that is potent at eradicating ALL in xenograft studies (Haso et al, Blood, 2013), by Targeting two antigens simultaneously could increase CAR potency and prevent antigen-loss escape. A Phase I clinical trial is currently enrolling patients at the NCI. 

NCI seeks co-development partners or licensees for dual-specific anti-CD22 anti-CD19 chimeric antigen receptors (CARs).



Potential Commercial Applications: Competitive Advantages:
  • Treatment of acute lymphoblastic leukemia (ALL), the most common form of cancer for children
  • Treatment of additional b cell malignancies including Diffuse Large B-Cell Lymphoma (DLBCL)
  • Adoptive immunotherapy
 
  • CAR-T has previously been demonstrated to be effective in the treatment of b cell malignances
  • Targeting two antigens on one CAR offers the advantage of better cancer cell targeting and reduces the possibility of antigen escape


Development Stage:
Clinical

Related Invention(s):
E-291-2012
E-080-2008
E-017-2017


Inventors:

Terry Fry (NCI)  ➽ more inventions...


Intellectual Property:
Application No. 15/559,485

Publications:
Shalabi H, et. al. Safety and efficacy of CD19/CD22 CAR T cells in children and young adults with relapsed/refractory ALL (Abstract)  PMID: 32286905
Qin H, et. al. Preclinical development of bivalent chimeric antigen receptors targeting both CD19 and CD22  PMID: 30581986

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-106-2015
Updated: Feb 24, 2021