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FcγR-Binding Is an Important Functional Attribute for Immune Checkpoint Antibodies in Cancer Immunotherapy
T cells play critical roles in anti-tumor immunity. Up-regulation of immune checkpoint molecules (PD-1, PD-L1, CTLA-4, TIM-3, Lag-3, TIGIT, CD73, VISTA, B7-H3) in the tumor microenvironment is an important mechanism that restrains effector T cells from the anti-tumor activity. To date, immune checkp...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399403/ https://www.ncbi.nlm.nih.gov/pubmed/30863404 http://dx.doi.org/10.3389/fimmu.2019.00292 |
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author | Chen, Xin Song, Xiaomin Li, Kang Zhang, Tong |
author_facet | Chen, Xin Song, Xiaomin Li, Kang Zhang, Tong |
author_sort | Chen, Xin |
collection | PubMed |
description | T cells play critical roles in anti-tumor immunity. Up-regulation of immune checkpoint molecules (PD-1, PD-L1, CTLA-4, TIM-3, Lag-3, TIGIT, CD73, VISTA, B7-H3) in the tumor microenvironment is an important mechanism that restrains effector T cells from the anti-tumor activity. To date, immune checkpoint antibodies have demonstrated significant clinical benefits for cancer patients treated with mono- or combination immunotherapies. However, many tumors do not respond to the treatment well, and merely blocking the immune suppression pathways by checkpoint-regulatory antibodies may not render optimal tumor growth inhibition. Binding of the antibody Fc-hinge region to Fc gamma receptors (FcγRs) has been shown to exert a profound impact on antibody function and in vivo efficacy. Investigation of immune checkpoint antibodies regarding their effector functions and impact on therapeutic efficacy has gained more attention in recent years. In this review, we discuss Fc variants of antibodies against immune checkpoint targets and the potential mechanisms of how FcγR-binding could influence the anti-tumor activity of these antibodies. |
format | Online Article Text |
id | pubmed-6399403 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63994032019-03-12 FcγR-Binding Is an Important Functional Attribute for Immune Checkpoint Antibodies in Cancer Immunotherapy Chen, Xin Song, Xiaomin Li, Kang Zhang, Tong Front Immunol Immunology T cells play critical roles in anti-tumor immunity. Up-regulation of immune checkpoint molecules (PD-1, PD-L1, CTLA-4, TIM-3, Lag-3, TIGIT, CD73, VISTA, B7-H3) in the tumor microenvironment is an important mechanism that restrains effector T cells from the anti-tumor activity. To date, immune checkpoint antibodies have demonstrated significant clinical benefits for cancer patients treated with mono- or combination immunotherapies. However, many tumors do not respond to the treatment well, and merely blocking the immune suppression pathways by checkpoint-regulatory antibodies may not render optimal tumor growth inhibition. Binding of the antibody Fc-hinge region to Fc gamma receptors (FcγRs) has been shown to exert a profound impact on antibody function and in vivo efficacy. Investigation of immune checkpoint antibodies regarding their effector functions and impact on therapeutic efficacy has gained more attention in recent years. In this review, we discuss Fc variants of antibodies against immune checkpoint targets and the potential mechanisms of how FcγR-binding could influence the anti-tumor activity of these antibodies. Frontiers Media S.A. 2019-02-26 /pmc/articles/PMC6399403/ /pubmed/30863404 http://dx.doi.org/10.3389/fimmu.2019.00292 Text en Copyright © 2019 Chen, Song, Li and Zhang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Chen, Xin Song, Xiaomin Li, Kang Zhang, Tong FcγR-Binding Is an Important Functional Attribute for Immune Checkpoint Antibodies in Cancer Immunotherapy |
title | FcγR-Binding Is an Important Functional Attribute for Immune Checkpoint Antibodies in Cancer Immunotherapy |
title_full | FcγR-Binding Is an Important Functional Attribute for Immune Checkpoint Antibodies in Cancer Immunotherapy |
title_fullStr | FcγR-Binding Is an Important Functional Attribute for Immune Checkpoint Antibodies in Cancer Immunotherapy |
title_full_unstemmed | FcγR-Binding Is an Important Functional Attribute for Immune Checkpoint Antibodies in Cancer Immunotherapy |
title_short | FcγR-Binding Is an Important Functional Attribute for Immune Checkpoint Antibodies in Cancer Immunotherapy |
title_sort | fcγr-binding is an important functional attribute for immune checkpoint antibodies in cancer immunotherapy |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399403/ https://www.ncbi.nlm.nih.gov/pubmed/30863404 http://dx.doi.org/10.3389/fimmu.2019.00292 |
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