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A Novel Bispecific Antibody Targeting CD3 and Lewis Y with Potent Therapeutic Efficacy against Gastric Cancer

Lewis Y antigen, a glycan highly expressed on most epithelial cancers, was targeted for cancer treatment but lacked satisfactory results in some intractable and refractory cancers. Thus, it is highly desirable to develop an effective therapy against these cancers, hopefully based on this target. In...

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Autores principales: Chen, Jie, Pan, Zhidi, Han, Lei, Zhou, Yuexian, Zong, Huifang, Wang, Lei, Sun, Rui, Jiang, Hua, Xie, Yueqing, Yuan, Yunsheng, Wu, Mingyuan, Bian, Yanling, Zhang, Baohong, Zhu, Jianwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393954/
https://www.ncbi.nlm.nih.gov/pubmed/34440263
http://dx.doi.org/10.3390/biomedicines9081059
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author Chen, Jie
Pan, Zhidi
Han, Lei
Zhou, Yuexian
Zong, Huifang
Wang, Lei
Sun, Rui
Jiang, Hua
Xie, Yueqing
Yuan, Yunsheng
Wu, Mingyuan
Bian, Yanling
Zhang, Baohong
Zhu, Jianwei
author_facet Chen, Jie
Pan, Zhidi
Han, Lei
Zhou, Yuexian
Zong, Huifang
Wang, Lei
Sun, Rui
Jiang, Hua
Xie, Yueqing
Yuan, Yunsheng
Wu, Mingyuan
Bian, Yanling
Zhang, Baohong
Zhu, Jianwei
author_sort Chen, Jie
collection PubMed
description Lewis Y antigen, a glycan highly expressed on most epithelial cancers, was targeted for cancer treatment but lacked satisfactory results in some intractable and refractory cancers. Thus, it is highly desirable to develop an effective therapy against these cancers, hopefully based on this target. In this work, we constructed a novel T cell-engaging bispecific antibody targeting Lewis Y and CD3 (m3s193 BsAb) with the IgG-[L]-scfv format. In vitro activity of m3s193 BsAb was evaluated by affinity assay to target cells, cytotoxicity assay, cytokines releasing assay, and T cells proliferation and recruiting assays. Anti-tumor activity against gastric cancer was evaluated in vivo by subcutaneous huPBMCs/tumor cells co-grafting model and huPBMCs intravenous injecting model. In vitro, m3s193 BsAb appeared to have a high binding affinity to Lewis Y positive cells and Jurkat cells. The BsAb showed stronger activity than its parent mAb in T cell recruiting, activation, proliferation, cytokine release, and cytotoxicity. In vivo, m3s193 BsAb not only demonstrated higher therapeutic efficacy in the huPBMCs/tumor co-grafting gastric carcinoma model than the parent mAb but also eliminated tumors in the model of intravenous injection with huPBMCs. Strong anti-tumor activity of m3s193 BsAb revealed that Lewis Y could be targeted in T cell-engaging BsAb for gastric cancer therapy.
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spelling pubmed-83939542021-08-28 A Novel Bispecific Antibody Targeting CD3 and Lewis Y with Potent Therapeutic Efficacy against Gastric Cancer Chen, Jie Pan, Zhidi Han, Lei Zhou, Yuexian Zong, Huifang Wang, Lei Sun, Rui Jiang, Hua Xie, Yueqing Yuan, Yunsheng Wu, Mingyuan Bian, Yanling Zhang, Baohong Zhu, Jianwei Biomedicines Article Lewis Y antigen, a glycan highly expressed on most epithelial cancers, was targeted for cancer treatment but lacked satisfactory results in some intractable and refractory cancers. Thus, it is highly desirable to develop an effective therapy against these cancers, hopefully based on this target. In this work, we constructed a novel T cell-engaging bispecific antibody targeting Lewis Y and CD3 (m3s193 BsAb) with the IgG-[L]-scfv format. In vitro activity of m3s193 BsAb was evaluated by affinity assay to target cells, cytotoxicity assay, cytokines releasing assay, and T cells proliferation and recruiting assays. Anti-tumor activity against gastric cancer was evaluated in vivo by subcutaneous huPBMCs/tumor cells co-grafting model and huPBMCs intravenous injecting model. In vitro, m3s193 BsAb appeared to have a high binding affinity to Lewis Y positive cells and Jurkat cells. The BsAb showed stronger activity than its parent mAb in T cell recruiting, activation, proliferation, cytokine release, and cytotoxicity. In vivo, m3s193 BsAb not only demonstrated higher therapeutic efficacy in the huPBMCs/tumor co-grafting gastric carcinoma model than the parent mAb but also eliminated tumors in the model of intravenous injection with huPBMCs. Strong anti-tumor activity of m3s193 BsAb revealed that Lewis Y could be targeted in T cell-engaging BsAb for gastric cancer therapy. MDPI 2021-08-20 /pmc/articles/PMC8393954/ /pubmed/34440263 http://dx.doi.org/10.3390/biomedicines9081059 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Jie
Pan, Zhidi
Han, Lei
Zhou, Yuexian
Zong, Huifang
Wang, Lei
Sun, Rui
Jiang, Hua
Xie, Yueqing
Yuan, Yunsheng
Wu, Mingyuan
Bian, Yanling
Zhang, Baohong
Zhu, Jianwei
A Novel Bispecific Antibody Targeting CD3 and Lewis Y with Potent Therapeutic Efficacy against Gastric Cancer
title A Novel Bispecific Antibody Targeting CD3 and Lewis Y with Potent Therapeutic Efficacy against Gastric Cancer
title_full A Novel Bispecific Antibody Targeting CD3 and Lewis Y with Potent Therapeutic Efficacy against Gastric Cancer
title_fullStr A Novel Bispecific Antibody Targeting CD3 and Lewis Y with Potent Therapeutic Efficacy against Gastric Cancer
title_full_unstemmed A Novel Bispecific Antibody Targeting CD3 and Lewis Y with Potent Therapeutic Efficacy against Gastric Cancer
title_short A Novel Bispecific Antibody Targeting CD3 and Lewis Y with Potent Therapeutic Efficacy against Gastric Cancer
title_sort novel bispecific antibody targeting cd3 and lewis y with potent therapeutic efficacy against gastric cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393954/
https://www.ncbi.nlm.nih.gov/pubmed/34440263
http://dx.doi.org/10.3390/biomedicines9081059
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