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Harnessing co-stimulatory TNF receptors for cancer immunotherapy: Current approaches and future opportunities

Jeremy D Waight, Randi B Gombos, Nicholas S Wilson

    Human Antibodies
    |January 14, 2017
    PubMed

    Insights

    Agonist antibodies targeting co-stimulatory tumor necrosis factor receptors (TNFRs) like CD137 can enhance anti-tumor immunity. Optimizing their design is key to maximizing therapeutic benefits while minimizing adverse events.

    Area of Science:

    • Immunology
    • Oncology
    • Pharmacology

    Background:

    • Co-stimulatory tumor necrosis factor receptors (TNFRs) play a crucial role in regulating T cell responses against tumor antigens.
    • Agonist antibodies targeting TNFRs such as CD137, CD357, CD134, and CD27 are being investigated for cancer immunotherapy.
    • Developing these antibodies presents challenges in balancing anti-tumor efficacy with immune-related adverse events.

    Purpose of the Study:

    • To review the expression, signaling, and structural characteristics of CD137, CD357, CD134, and CD27.
    • To explore how this knowledge can inform the design of effective immuno-modulatory antibodies targeting these receptors.
    • To discuss the role of Fc gamma receptors (FcγRs) in antibody-mediated TNFR activation and immune responses.

    Main Methods:

    • Literature review of preclinical and clinical data on co-stimulatory TNFR antibodies.
    • Analysis of receptor expression, signaling pathways, and structural features.
    • Integration of emerging knowledge on FcγR interactions.

    Main Results:

    • Co-stimulatory TNFRs are critical for sculpting T cell responses to tumor antigens.
    • Understanding receptor biology and FcγR interactions can guide the design of next-generation TNFR-targeting antibodies.
    • Current research focuses on optimizing antibody design for enhanced anti-tumor immunity and reduced toxicity.

    Conclusions:

    • Co-stimulatory TNFR antibodies hold significant therapeutic potential in cancer immunotherapy.
    • Informed antibody design, considering receptor features and FcγR engagement, is essential for clinical success.
    • Future efforts should focus on developing next-generation molecules with improved pharmacological properties for better patient outcomes.
    Keywords:
    4-1BBCD134CD137CD27CD357FcγRGITROX40TNFRTNFRSFTRAFantibodiescancerclinical trialsco-stimulationhumanimmunotherapyoncology

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