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High affinity monoclonal antibody targeting Siglec-15 for cancer immunotherapy

BACKGROUND AND AIM: Recently, Siglec-15 has been proved as a novel immune suppressor and a potential target for normalization cancer immunotherapy, which is non-redundant to the well-known PD-L1/PD-1 pathway. Herein, anti-Siglec-15 mAb, a monoclonal antibody (mAb) with a high affinity against Siglec...

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Autores principales: He, Fei, Wang, Na, Li, Jiangwei, He, Luanying, Yang, Zhao, Lu, Jiandong, Xiong, Guoliang, Yu, Changyuan, Wang, Shihui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Whioce Publishing Pte. Ltd. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710358/
https://www.ncbi.nlm.nih.gov/pubmed/34988324
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author He, Fei
Wang, Na
Li, Jiangwei
He, Luanying
Yang, Zhao
Lu, Jiandong
Xiong, Guoliang
Yu, Changyuan
Wang, Shihui
author_facet He, Fei
Wang, Na
Li, Jiangwei
He, Luanying
Yang, Zhao
Lu, Jiandong
Xiong, Guoliang
Yu, Changyuan
Wang, Shihui
author_sort He, Fei
collection PubMed
description BACKGROUND AND AIM: Recently, Siglec-15 has been proved as a novel immune suppressor and a potential target for normalization cancer immunotherapy, which is non-redundant to the well-known PD-L1/PD-1 pathway. Herein, anti-Siglec-15 mAb, a monoclonal antibody (mAb) with a high affinity against Siglec-15, was prepared. METHODS: The engineered CHO-K1 Siglec-15 cell line was constructed to heterologously expressed Siglec-15 for the affinity test with the mAb. Antigens Siglec-15-mIgG and Siglec-15-his were recombinantly expressed by 293F cells and purified by high-performance liquid chromatography (HPLC). Hybridoma cell line against Siglec-15 was prepared and validated by enzyme-linked immunoabsorbant assay (ELISA) and fluorescent-activated cell sorting (FACS). Finally, the anti-Siglec-15 mAb was produced, purified, and confirmed by SDS-PAGE, ELISA, and FACS. RESULTS: The EC(50) of the anti-Siglec-15 mAb with Siglec-15 is 76.65 ng/mL, lower than that of the positive control 5G12 (90.7 ng/mL), indicating a high affinity of the anti-Siglec-15 mAb. In vitro and in vivo studies verified that the anti-Siglec-15 mAb blocks the Siglec-15-mediated suppression of T cell and moderately prevents the tumor growth. CONCLUSIONS: The anti-Siglec-15 mAb can be considered as an effective immunotherapy for tumor suppression. RELEVANCE FOR PATIENTS: The anti-Siglec-15 mAb prepared in this study is useful as an immune checkpoint inhibitor against Siglec-15 for normalization cancer immunotherapy. This immunotherapy provides an alternative treatment for cancer patients who are refractory to the well-known PD-L1/PD-1-targeting therapies.
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spelling pubmed-87103582022-01-04 High affinity monoclonal antibody targeting Siglec-15 for cancer immunotherapy He, Fei Wang, Na Li, Jiangwei He, Luanying Yang, Zhao Lu, Jiandong Xiong, Guoliang Yu, Changyuan Wang, Shihui J Clin Transl Res Original Article BACKGROUND AND AIM: Recently, Siglec-15 has been proved as a novel immune suppressor and a potential target for normalization cancer immunotherapy, which is non-redundant to the well-known PD-L1/PD-1 pathway. Herein, anti-Siglec-15 mAb, a monoclonal antibody (mAb) with a high affinity against Siglec-15, was prepared. METHODS: The engineered CHO-K1 Siglec-15 cell line was constructed to heterologously expressed Siglec-15 for the affinity test with the mAb. Antigens Siglec-15-mIgG and Siglec-15-his were recombinantly expressed by 293F cells and purified by high-performance liquid chromatography (HPLC). Hybridoma cell line against Siglec-15 was prepared and validated by enzyme-linked immunoabsorbant assay (ELISA) and fluorescent-activated cell sorting (FACS). Finally, the anti-Siglec-15 mAb was produced, purified, and confirmed by SDS-PAGE, ELISA, and FACS. RESULTS: The EC(50) of the anti-Siglec-15 mAb with Siglec-15 is 76.65 ng/mL, lower than that of the positive control 5G12 (90.7 ng/mL), indicating a high affinity of the anti-Siglec-15 mAb. In vitro and in vivo studies verified that the anti-Siglec-15 mAb blocks the Siglec-15-mediated suppression of T cell and moderately prevents the tumor growth. CONCLUSIONS: The anti-Siglec-15 mAb can be considered as an effective immunotherapy for tumor suppression. RELEVANCE FOR PATIENTS: The anti-Siglec-15 mAb prepared in this study is useful as an immune checkpoint inhibitor against Siglec-15 for normalization cancer immunotherapy. This immunotherapy provides an alternative treatment for cancer patients who are refractory to the well-known PD-L1/PD-1-targeting therapies. Whioce Publishing Pte. Ltd. 2021-11-16 /pmc/articles/PMC8710358/ /pubmed/34988324 Text en Copyright: © Whioce Publishing Pte. Ltd. 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-NC-ND 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
He, Fei
Wang, Na
Li, Jiangwei
He, Luanying
Yang, Zhao
Lu, Jiandong
Xiong, Guoliang
Yu, Changyuan
Wang, Shihui
High affinity monoclonal antibody targeting Siglec-15 for cancer immunotherapy
title High affinity monoclonal antibody targeting Siglec-15 for cancer immunotherapy
title_full High affinity monoclonal antibody targeting Siglec-15 for cancer immunotherapy
title_fullStr High affinity monoclonal antibody targeting Siglec-15 for cancer immunotherapy
title_full_unstemmed High affinity monoclonal antibody targeting Siglec-15 for cancer immunotherapy
title_short High affinity monoclonal antibody targeting Siglec-15 for cancer immunotherapy
title_sort high affinity monoclonal antibody targeting siglec-15 for cancer immunotherapy
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710358/
https://www.ncbi.nlm.nih.gov/pubmed/34988324
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