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Discovery of Anti-PD-L1 Human Domain Antibodies for Cancer Immunotherapy

Immunotherapy using monoclonal antibodies targeting the PD-1/PD-L1 interaction has shown enormous success for various cancers. Despite their encouraging results in clinics, antibody-based checkpoint inhibitors have several limitations, such as poor tumor penetration. To address these limitations of...

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Autores principales: Liu, Hao, Liu, Yanli, Zhao, Zhen, Li, Yuanke, Mustafa, Bahaa, Chen, Zhijin, Barve, Ashutosh, Jain, Akshay, Yao, Xiaolan, Li, Guangfu, Cheng, Kun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9013927/
https://www.ncbi.nlm.nih.gov/pubmed/35444660
http://dx.doi.org/10.3389/fimmu.2022.838966
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author Liu, Hao
Liu, Yanli
Zhao, Zhen
Li, Yuanke
Mustafa, Bahaa
Chen, Zhijin
Barve, Ashutosh
Jain, Akshay
Yao, Xiaolan
Li, Guangfu
Cheng, Kun
author_facet Liu, Hao
Liu, Yanli
Zhao, Zhen
Li, Yuanke
Mustafa, Bahaa
Chen, Zhijin
Barve, Ashutosh
Jain, Akshay
Yao, Xiaolan
Li, Guangfu
Cheng, Kun
author_sort Liu, Hao
collection PubMed
description Immunotherapy using monoclonal antibodies targeting the PD-1/PD-L1 interaction has shown enormous success for various cancers. Despite their encouraging results in clinics, antibody-based checkpoint inhibitors have several limitations, such as poor tumor penetration. To address these limitations of monoclonal antibodies, there is a growing interest in developing low-molecular-weight checkpoint inhibitors, such as antibody fragments. Several antibody fragments targeting PD-1/PD-L1 were recently discovered using phage libraries from camel or alpaca. However, animal-derived antibody fragments may elicit unwanted immune responses, which limit their therapeutic applications. For the first time, we used a human domain antibody phage library and discovered anti-human PD-L1 human single-domain antibodies (dAbs) that block the PD-1/PD-L1 interaction. Among them, the CLV3 dAb shows the highest affinity to PD-L1. The CLV3 dAb also exhibits the highest blocking efficacy of the PD-1/PD-L1 interaction. Moreover, the CLV3 dAb significantly inhibits tumor growth in mice implanted with CT26 colon carcinoma cells. These results suggest that CLV3 dAb can be potentially used as an anti-PD-L1 inhibitor for cancer immunotherapy.
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spelling pubmed-90139272022-04-19 Discovery of Anti-PD-L1 Human Domain Antibodies for Cancer Immunotherapy Liu, Hao Liu, Yanli Zhao, Zhen Li, Yuanke Mustafa, Bahaa Chen, Zhijin Barve, Ashutosh Jain, Akshay Yao, Xiaolan Li, Guangfu Cheng, Kun Front Immunol Immunology Immunotherapy using monoclonal antibodies targeting the PD-1/PD-L1 interaction has shown enormous success for various cancers. Despite their encouraging results in clinics, antibody-based checkpoint inhibitors have several limitations, such as poor tumor penetration. To address these limitations of monoclonal antibodies, there is a growing interest in developing low-molecular-weight checkpoint inhibitors, such as antibody fragments. Several antibody fragments targeting PD-1/PD-L1 were recently discovered using phage libraries from camel or alpaca. However, animal-derived antibody fragments may elicit unwanted immune responses, which limit their therapeutic applications. For the first time, we used a human domain antibody phage library and discovered anti-human PD-L1 human single-domain antibodies (dAbs) that block the PD-1/PD-L1 interaction. Among them, the CLV3 dAb shows the highest affinity to PD-L1. The CLV3 dAb also exhibits the highest blocking efficacy of the PD-1/PD-L1 interaction. Moreover, the CLV3 dAb significantly inhibits tumor growth in mice implanted with CT26 colon carcinoma cells. These results suggest that CLV3 dAb can be potentially used as an anti-PD-L1 inhibitor for cancer immunotherapy. Frontiers Media S.A. 2022-04-04 /pmc/articles/PMC9013927/ /pubmed/35444660 http://dx.doi.org/10.3389/fimmu.2022.838966 Text en Copyright © 2022 Liu, Liu, Zhao, Li, Mustafa, Chen, Barve, Jain, Yao, Li and Cheng https://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
Liu, Hao
Liu, Yanli
Zhao, Zhen
Li, Yuanke
Mustafa, Bahaa
Chen, Zhijin
Barve, Ashutosh
Jain, Akshay
Yao, Xiaolan
Li, Guangfu
Cheng, Kun
Discovery of Anti-PD-L1 Human Domain Antibodies for Cancer Immunotherapy
title Discovery of Anti-PD-L1 Human Domain Antibodies for Cancer Immunotherapy
title_full Discovery of Anti-PD-L1 Human Domain Antibodies for Cancer Immunotherapy
title_fullStr Discovery of Anti-PD-L1 Human Domain Antibodies for Cancer Immunotherapy
title_full_unstemmed Discovery of Anti-PD-L1 Human Domain Antibodies for Cancer Immunotherapy
title_short Discovery of Anti-PD-L1 Human Domain Antibodies for Cancer Immunotherapy
title_sort discovery of anti-pd-l1 human domain antibodies for cancer immunotherapy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9013927/
https://www.ncbi.nlm.nih.gov/pubmed/35444660
http://dx.doi.org/10.3389/fimmu.2022.838966
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