Acute lymphoblastic leukemia (ALL) is the most common cancer in children with approximately 3,250 new cases occurring per year in the United States. About 20% of cases are refractory to current treatment protocols and there is a desperate need for targeted therapies that do not result in adverse side effects such as cognitive impairment.
The Interleukin-7 receptor-α (IL-7Rα) was identified as a major pathway driving T-cell derived ALL (T-ALL). Researchers at the National Cancer Institute (NCI) developed antibodies selectively targeting IL-7Rα. Two lead antibody candidates, designated 4A10 and 2B8, selectively bind IL-7Rα with nanomolar affinity. Each lead antibody mediates leukemic cell killing by antibody-dependent cellular cytotoxicity (ADCC) and causes a significant reduction in T-ALL cell burden when administered in a xenograft mouse model harboring patient derived leukemia. Tumor reduction occurred despite the absence of ADCC immune effector cells in the xenograft mouse model. Furthermore, a synergistic effect occurred when combining the IL-7Rα antibody with AMD3100, a commercially available CXCR4 antagonist approved as a therapeutic in humans. The combination treatment resulted in a significant improvement in clearance of T-ALL cell burden in a xenograft mouse model.
The National Cancer Institute (NCI) seeks licensing and/or co-development research collaborations for the further development of these IL-7Rα-selective antibodies as targeted therapies for a range of indications including oncology and autoimmune disorders. Examples include cell acute lymphoblastic leukemia (T-ALL), B-cell acute lymphoblastic leukemia (B-ALL), several autoimmune disorders (Type 1 diabetes and multiple sclerosis) and organ transplant rejection.