Neuritin Impact T Cell Tolerance Induction and Maintenance and is a Target for Tumor Immunotherapy

Unmet Need
Cancer immunotherapy is a therapeutic approach that has revolutionized advanced cancer treatment. In particular, the use of therapeutic blocking antibodies to cytotoxic T-lymphocyte antigen 4 (CTLA4) and programmed cell death protein (PD-1) has achieved routine clinical use in numerous indications. Despite these promising results, monotherapy with either PD-1 of CTLA4 blockade have limited efficacy in the treatment of less immunogenic tumors. Consequently, novel therapeutic targets that effectively increase antitumor immunity and synergize with PD-1 and CTLA4 therapy would have widespread clinical utility.  
 
Technology Overview
The inventors have identified a novel target for immunotherapy, neuritin (Nrn1). The inventors found that Nrn1 promotes immune tolerance, by promoting T cell anergy and increasing the production and suppressive function of regulatory T cells. The inventors found that tumors in Nrn-1 deficient mice had inhibited tumor growth. The inventors tested the function of antibodies to nrn1 in a mouse model of B16F10 melanoma, a poorly immunogenic tumor, and found that this approach inhibited cancer growth as a monotherapy and enhanced the anti-tumor efficacy of combination therapy with anti-CTLA4 and anti-PD1 therapy,
 
Stage of Development
The inventors have tested mouse and human Nrn1-specific monoclonal antibodies and shown anti-tumor efficacy in numerous preclinical models.
 
Publications
JJ Barbi et al. J Immunol, 2016, 196 (1 Supplement) 58.12.
 

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