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IL7Rα-Specific Antibody for Treating Acute Lymphoblastic Leukemia (ALL)

Summary
The National Cancer Institute seeks licensing and/or co-development research collaborations for further development of antibodies that selectively target IL-7Rα, a major driver of T-cell derived ALL (T-ALL) and an important therapeutic target for a range of diseases.
NIH Reference Number
E-247-2015
Product Type
Keywords
  • Cancer, Therapy, Personalized Medicine, Targeted Therapy, Antibody, Antibody-Dependent Cellular Cytotoxicity (ADCC), Acute lymphoblastic leukemia (ALL), Autoimmunity, Diabetes, Multiple Sclerosis, Transplantation, Interleukin-7 receptor-α (IL-7Rα), Durum
Collaboration Opportunity
This invention is available for licensing and co-development.
Contact
Description of Technology

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.

Potential Commercial Applications
  • Targeted therapy for various cancers including T-cell acute lymphoblastic leukemia (T-ALL) and B-cell acute lymphoblastic leukemia (B-ALL)
  • Targeted therapy for several autoimmune disorders (Type 1 diabetes and multiple sclerosis), organ transplant rejection, Type 1 diabetes, and multiple sclerosis
Competitive Advantages
  • Selectively bind IL-7Rα with high (nanomolar) affinity
  • Mediates cancer cell killing through antibody-dependent cellular cytotoxicity (ADCC)
  • Targeted therapy with potential for fewer and less severe adverse events
  • Well-established regulatory path
  • Numerous approved products using same approach (e.g., Rituximab, and Cetuximab)
Inventor(s)

Scott Durum (NCI), Julie Hixon (NCI), Wenqing Li (NCI), Scott Walsh (NCI), Lila Kashi (NCI)

Development Stage
Patent Status
  • U.S. Provisional: U.S. Provisional Patent Application Number 62/238,612, Filed 07 Oct 2015
  • U.S. Patent Filed: U.S. Patent Application Number PCT/US2016/055957, Filed 07 Oct 2016
Therapeutic Area
Updated
Wednesday, January 17, 2018