Related Experiment Video

Updated: Jul 9, 2025

Assessment of Human Natural Killer Cell Events Driven by FcγRIIIa Engagement in the Presence of Therapeutic Antibodies
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Assessment of Human Natural Killer Cell Events Driven by FcγRIIIa Engagement in the Presence of Therapeutic Antibodies

Published on: May 22, 2020

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Fcγ receptors and immunomodulatory antibodies in cancer

Felipe Galvez-Cancino1,2, Alexander P Simpson1,2, Cristobal Costoya1

  • 1Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London, UK.

Nature Reviews. Cancer
|December 7, 2023
PubMed

Insights

Immunomodulatory antibodies harness Fc-FcγR interactions for cancer immunity. Engineering these interactions and understanding Fc receptor variability are key for next-generation cancer immunotherapies.

Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) inhibitors are key cancer immunotherapies.
  • Antibody efficacy relies on target engagement and Fc-Fcγ receptor (FcγR) interactions, crucial for antibody-dependent cell-mediated cytotoxicity.
  • FcγR roles in immunomodulatory antibodies are less understood than in tumor-targeting antibodies.

Purpose of the Study:

  • To review the contribution of FcγRs to the in vivo activity of immunomodulatory antibodies.
  • To discuss challenges in translating preclinical findings to clinical applications.
  • To explore the impact of human FcγR genetic variability on therapeutic antibody activity and future antibody engineering.

Main Methods:

  • Literature review of preclinical and clinical studies on Fc-FcγR interactions in cancer immunotherapy.
  • Analysis of existing data on the impact of FcγR polymorphisms on therapeutic antibody efficacy.
  • Discussion of antibody engineering strategies to optimize Fc-FcγR engagement.

Main Results:

  • Fc-FcγR interactions significantly influence the efficacy of both tumor-targeting and immunomodulatory antibodies.
  • Preclinical models show FcγR engagement is critical, but clinical translation faces challenges.
  • Genetic variations in human FcγRs can modulate therapeutic antibody responses.

Conclusions:

  • Fc-FcγR interactions are a critical but complex component of cancer immunotherapy.
  • Further research and antibody engineering are needed to optimize FcγR engagement for enhanced therapeutic outcomes.
  • Understanding FcγR variability is essential for personalized cancer immunotherapy.

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