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).
- 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
- 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