Asset

  • No.

    138

  • Asset Title

    Monoamine Oxidase Blockade Therapy for Treating Cancer

  • Organization

    University of California - Los Angeles

  • Product Type

    Small molecule

  • Therapeutic Area

    Oncology

  • Development Stage

    Hit To Lead or Lead Optimization

  • Technical Summary

    • MAO-A acts as an inhibitor of antitumor CD8 T Cell response, and also polarizes tumor-associated macrophages (TAMs) for immune suppression in a solid tumor.

    • Targeting tumor-associated macrophages (TAMs) is a promising strategy to modify the immunosuppressive tumor microenvironment and improve cancer immunotherapy. Mono-amineoxidase A (MAO-A) is an enzyme best known for its function in the brain; small molecule MAO inhibitors (MAOIs) are clinically used for treating neurological disorders. 

    • MAO-A induction in mouse and human TAMs. MAO-A-deficient mice exhibit decreased TAM immunosuppressive functions corresponding with enhanced antitumor immunity. MAOI treatment induces TAM reprogramming and suppresses tumor growth in preclinical mouse syngeneic and human xenograft tumor models. 

    • Combining MAOI and anti-PD-1 treatments results in synergistic tumor suppression. Clinical data correlation studies associate high intra-tumoral MAO-A expression with poor patient survival in a broad range of cancers. 

    • MAO-A promotes TAM immunosuppressive polarization via upregulating oxidative stress. Together, these data identify MAO-A as a critical regulator of TAMs and support repurposing MAOIs for TAM reprogramming to improve cancer immunotherapy. 

  • Patent

    WO2022087361A1

  • Publication

    Targeting monoamine oxidase A-regulated tumor-associated macrophage polarization for cancer immunotherapy, Nature Communications. (2021)

  • Attachment

TOP