- Jim Knabb
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).
- 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
Terry Fry M.D. (NCI)
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]
- U.S. Patent Filed: U.S. Patent Application Number 15/559,485 , Filed 19 Sep 2017