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Fcγ receptors and immunomodulatory antibodies in cancer

Galvez-Cancino, Felipe; Simpson, Alexander P; Costoya, Cristobal; Matos, Ignacio; Qian, Danwen; Peggs, Karl S; Litchfield, Kevin; (2023) Fcγ receptors and immunomodulatory antibodies in cancer. Nature Reviews Cancer , 24 (1) pp. 51-71. 10.1038/s41568-023-00637-8. Green open access

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Abstract

The discovery of both cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) as negative regulators of antitumour immunity led to the development of numerous immunomodulatory antibodies as cancer treatments. Preclinical studies have demonstrated that the efficacy of immunoglobulin G (IgG)-based therapies depends not only on their ability to block or engage their targets but also on the antibody's constant region (Fc) and its interactions with Fcγ receptors (FcγRs). Fc-FcγR interactions are essential for the activity of tumour-targeting antibodies, such as rituximab, trastuzumab and cetuximab, where the killing of tumour cells occurs at least in part due to these mechanisms. However, our understanding of these interactions in the context of immunomodulatory antibodies designed to boost antitumour immunity remains less explored. In this Review, we discuss our current understanding of the contribution of FcγRs to the in vivo activity of immunomodulatory antibodies and the challenges of translating results from preclinical models into the clinic. In addition, we review the impact of genetic variability of human FcγRs on the activity of therapeutic antibodies and how antibody engineering is being utilized to develop the next generation of cancer immunotherapies.

Type: Article
Title: Fcγ receptors and immunomodulatory antibodies in cancer
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41568-023-00637-8
Publisher version: http://dx.doi.org/10.1038/s41568-023-00637-8
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Humans, Receptors, IgG, Immunoglobulin G, Immunomodulation, Immunotherapy, Neoplasms
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10186257
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