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How to select IgG subclasses in developing anti-tumor therapeutic antibodies

The intact antibody of human immunoglobulin (IgG) is composed of the fragment for antigen binding (Fab) and the crystallizable fragment (Fc) for binding of Fcγ receptors. Among the four subclasses of human IgG (IgG1, IgG2, IgG3, IgG4), which differ in their constant regions, particularly in their hi...

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Autores principales: Yu, Jifeng, Song, Yongping, Tian, Wenzhi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201658/
https://www.ncbi.nlm.nih.gov/pubmed/32370812
http://dx.doi.org/10.1186/s13045-020-00876-4
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author Yu, Jifeng
Song, Yongping
Tian, Wenzhi
author_facet Yu, Jifeng
Song, Yongping
Tian, Wenzhi
author_sort Yu, Jifeng
collection PubMed
description The intact antibody of human immunoglobulin (IgG) is composed of the fragment for antigen binding (Fab) and the crystallizable fragment (Fc) for binding of Fcγ receptors. Among the four subclasses of human IgG (IgG1, IgG2, IgG3, IgG4), which differ in their constant regions, particularly in their hinges and CH2 domains, IgG1 has the highest FcγR-binding affinity, followed by IgG3, IgG2, and IgG4. As a result, different subclasses have different effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Fcγ receptors include six subtypes (FcγRI, FcγRIIA, FcγRIIB, FcγRIIC, FcγRIIIA, FcγRIIIB) which differ in cellular distribution, binding affinity to Fc, and the resulting biological activity. Therefore, when developing anti-tumor therapeutic antibodies, including single-targeted antibodies, bi-specific antibodies (BsAbs), and antibody-drug conjugates (ADCs), many factors, such as target biology, cellular distribution of the targets, the environments of particular tumor types, as well as the proposed mechanism of action (MOA), must be taken into consideration. This review outlines fundamental strategies that are required to select IgG subclasses in developing anti-tumor therapeutic antibodies.
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spelling pubmed-72016582020-05-08 How to select IgG subclasses in developing anti-tumor therapeutic antibodies Yu, Jifeng Song, Yongping Tian, Wenzhi J Hematol Oncol Review The intact antibody of human immunoglobulin (IgG) is composed of the fragment for antigen binding (Fab) and the crystallizable fragment (Fc) for binding of Fcγ receptors. Among the four subclasses of human IgG (IgG1, IgG2, IgG3, IgG4), which differ in their constant regions, particularly in their hinges and CH2 domains, IgG1 has the highest FcγR-binding affinity, followed by IgG3, IgG2, and IgG4. As a result, different subclasses have different effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Fcγ receptors include six subtypes (FcγRI, FcγRIIA, FcγRIIB, FcγRIIC, FcγRIIIA, FcγRIIIB) which differ in cellular distribution, binding affinity to Fc, and the resulting biological activity. Therefore, when developing anti-tumor therapeutic antibodies, including single-targeted antibodies, bi-specific antibodies (BsAbs), and antibody-drug conjugates (ADCs), many factors, such as target biology, cellular distribution of the targets, the environments of particular tumor types, as well as the proposed mechanism of action (MOA), must be taken into consideration. This review outlines fundamental strategies that are required to select IgG subclasses in developing anti-tumor therapeutic antibodies. BioMed Central 2020-05-05 /pmc/articles/PMC7201658/ /pubmed/32370812 http://dx.doi.org/10.1186/s13045-020-00876-4 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Review
Yu, Jifeng
Song, Yongping
Tian, Wenzhi
How to select IgG subclasses in developing anti-tumor therapeutic antibodies
title How to select IgG subclasses in developing anti-tumor therapeutic antibodies
title_full How to select IgG subclasses in developing anti-tumor therapeutic antibodies
title_fullStr How to select IgG subclasses in developing anti-tumor therapeutic antibodies
title_full_unstemmed How to select IgG subclasses in developing anti-tumor therapeutic antibodies
title_short How to select IgG subclasses in developing anti-tumor therapeutic antibodies
title_sort how to select igg subclasses in developing anti-tumor therapeutic antibodies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201658/
https://www.ncbi.nlm.nih.gov/pubmed/32370812
http://dx.doi.org/10.1186/s13045-020-00876-4
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