Summary: 

The NCI seeks research co-development partners or licensees for Nucleophosmin 1 (NPM1) Mutation-Specific T Cell Receptors for Targeted Treatment of Acute Myeloid Leukemia.

Description of Technology: 

Acute myeloid leukemia (AML) is a rare form of blood cancer affecting myeloid stem and progenitor cells, associated with a poor prognosis and a 5-year survival rate of ~33%. Current treatments, including intensive chemotherapy and stem cell transplantation, are not suitable for all patients and can cause significant toxicities, including low blood cell counts, infection and graft-versus-host disease. Therefore, there is a need for safer and more effective treatments. 

This specific invention concerns the isolation of two highly specific T cell receptors (TCRs), known as TCR6 and TCR7, recognizing a neoepitope, AVEEVSLRK. The neoepitope is derived from mutant Nucleophosmin 1 (NPM1) and presented in the context of HLA-A*11:01. Pre-clinical results for these TCRs revealed robust and specific cytotoxicity against a leukemia cell line and several patient-derived AML samples expressing the NPM1 mutation and HLA-A*11:01. Furthermore, they showed no cross-reactivity to normal peripheral blood mononuclear cells, structurally similar peptides or unrelated HLA alleles. These results suggest these novel TCRs represent a potential adoptive T cell therapy for the treatment of AML.

Potential Commercial Applications: 

• Acute myeloid leukemia patients expressing HLA-A*11:01. 

Competitive Advantages:

• Highly specific targeting of mutant NPM1
• Minimed off-target effects with enhanced safety profile
• •Significant unmet medical need for AML patients