Synergistic Combination of Immunologic Inhibitors for the Treatment of Cancer



    • Monotherapy treatment with cancer immunotherapies limits treatment efficacy by accelerating the development of drug resistance and promoting the hyper-regulation of analogous un-drugged pathways. These shortcomings can potentially be addressed by synergistically combining multiple immunotherapy drugs into a single treatment regimen.
    • The inventors demonstrated that simultaneously blocking multiple immune regulatory pathways (CTLA-4, PD-L1, IDO) in various combinations improved tumor control in vivo. Therefore, using combinations of FDA approved inhibitors of these pathways may boost efficacy over treatment with single therapies.
    • The invention is a treatment approach for multiple types of cancer that combines FDA approved antibodies targeting CTLA-4, PD-L1, and IDO. Simultaneously blocking these pathways promotes tumor CD8+ T cell response and natural IL-2 activity, driving a stronger anti-tumor immune response than each of these treatments alone. 
    • The drug combinations were evaluated in an in vivo mouse model of melanoma (CTLA-4+PD-L1, CTLA-4+IDO, PD-L1+IDO) and showed markedly improved tumor control over single treatment, with some mice achieving complete tumor rejection. A significant increase in IL-2 production by tumor infiltrating CD8+ T cells was observed just 3 days after treatment initiation.



    The three combinations of immune inhibitors tested (shaded circle) each showed an improvement in tumor size reduction as compared to monotherapy treatment (triangle and diamond) when evaluated in mouse models of melanoma.





    • Improved efficacy over monotherapy
    • Effective in mature tumors
    • Invigorates T-cell polyfunctionality.



    • Cancer immunotherapy
    • Predictive biomarkers
    • Drug repurposing/combination therapy





    • US: 10,034,939
    • Counterparts pending in the EU and Canada



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