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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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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. |
format | Online Article Text |
id | pubmed-9013927 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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