A Novel Anti-B7-H3 × Anti-CD3 Bispecific Antibody with Potent Antitumor Activity
B7-H3 plays an important role in tumor apoptosis, proliferation, adhesion, angiogenesis, invasion, migration, and evasion of immune surveillance. It is overexpressed in various human solid tumor tissues. In patients, B7-H3 overexpression correlates with advanced stages, poor clinical outcomes, and r...
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| Format: | Article |
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MDPI AG
2022-01-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/12/2/157 |
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| author | Yan Feng Kun Xie Yanxin Yin Bingyu Li Chenyu Pi Xiaoqing Xu Tao Huang Jingming Zhang Bo Wang Hua Gu Jianmin Fang |
| author_facet | Yan Feng Kun Xie Yanxin Yin Bingyu Li Chenyu Pi Xiaoqing Xu Tao Huang Jingming Zhang Bo Wang Hua Gu Jianmin Fang |
| author_sort | Yan Feng |
| collection | DOAJ |
| description | B7-H3 plays an important role in tumor apoptosis, proliferation, adhesion, angiogenesis, invasion, migration, and evasion of immune surveillance. It is overexpressed in various human solid tumor tissues. In patients, B7-H3 overexpression correlates with advanced stages, poor clinical outcomes, and resistance to therapy. The roles of B7-H3 in tumor progression make it a potential candidate for targeted therapy. Here, we generated a mouse anti-human B7-H3 antibody and demonstrated its binding activity via Tongji University Suzhou Instituteprotein-based and cell-based assays. We then developed a novel format anti-B7-H3 × anti-CD3 bispecific antibody based on the antibody-binding fragment of the anti-B7-H3 antibody and single-chain variable fragment structure of anti-CD3 antibody (OKT3) and demonstrated that this bispecific antibody mediated potent cytotoxic activities against various B7-H3-positive tumor cell lines in vitro by improving T cell activation and proliferation. This bispecific antibody also demonstrated potent antitumor activity in humanized mice xenograft models. These results revealed that the novel anti-B7-H3 × anti-CD3 bispecific antibody has the potential to be employed in treatment of B7-H3-positive solid tumors. |
| first_indexed | 2024-03-09T21:34:58Z |
| format | Article |
| id | doaj.art-0900734a0f11490cbfb341f554ed551e |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-09T21:34:58Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-0900734a0f11490cbfb341f554ed551e2023-11-23T20:45:03ZengMDPI AGLife2075-17292022-01-0112215710.3390/life12020157A Novel Anti-B7-H3 × Anti-CD3 Bispecific Antibody with Potent Antitumor ActivityYan Feng0Kun Xie1Yanxin Yin2Bingyu Li3Chenyu Pi4Xiaoqing Xu5Tao Huang6Jingming Zhang7Bo Wang8Hua Gu9Jianmin Fang10School of Life Sciences and Technology, Tongji University, Shanghai 200092, ChinaSchool of Life Sciences and Technology, Tongji University, Shanghai 200092, ChinaSchool of Life Sciences and Technology, Tongji University, Shanghai 200092, ChinaSchool of Life Sciences and Technology, Tongji University, Shanghai 200092, ChinaSchool of Life Sciences and Technology, Tongji University, Shanghai 200092, ChinaSchool of Life Sciences and Technology, Tongji University, Shanghai 200092, ChinaSchool of Life Sciences and Technology, Tongji University, Shanghai 200092, ChinaSchool of Life Sciences and Technology, Tongji University, Shanghai 200092, ChinaSchool of Life Sciences and Technology, Tongji University, Shanghai 200092, ChinaSchool of Life Sciences and Technology, Tongji University, Shanghai 200092, ChinaSchool of Life Sciences and Technology, Tongji University, Shanghai 200092, ChinaB7-H3 plays an important role in tumor apoptosis, proliferation, adhesion, angiogenesis, invasion, migration, and evasion of immune surveillance. It is overexpressed in various human solid tumor tissues. In patients, B7-H3 overexpression correlates with advanced stages, poor clinical outcomes, and resistance to therapy. The roles of B7-H3 in tumor progression make it a potential candidate for targeted therapy. Here, we generated a mouse anti-human B7-H3 antibody and demonstrated its binding activity via Tongji University Suzhou Instituteprotein-based and cell-based assays. We then developed a novel format anti-B7-H3 × anti-CD3 bispecific antibody based on the antibody-binding fragment of the anti-B7-H3 antibody and single-chain variable fragment structure of anti-CD3 antibody (OKT3) and demonstrated that this bispecific antibody mediated potent cytotoxic activities against various B7-H3-positive tumor cell lines in vitro by improving T cell activation and proliferation. This bispecific antibody also demonstrated potent antitumor activity in humanized mice xenograft models. These results revealed that the novel anti-B7-H3 × anti-CD3 bispecific antibody has the potential to be employed in treatment of B7-H3-positive solid tumors.https://www.mdpi.com/2075-1729/12/2/157B7-H3bispecific T cell engagersolid tumorimmunotherapy |
| spellingShingle | Yan Feng Kun Xie Yanxin Yin Bingyu Li Chenyu Pi Xiaoqing Xu Tao Huang Jingming Zhang Bo Wang Hua Gu Jianmin Fang A Novel Anti-B7-H3 × Anti-CD3 Bispecific Antibody with Potent Antitumor Activity Life B7-H3 bispecific T cell engager solid tumor immunotherapy |
| title | A Novel Anti-B7-H3 × Anti-CD3 Bispecific Antibody with Potent Antitumor Activity |
| title_full | A Novel Anti-B7-H3 × Anti-CD3 Bispecific Antibody with Potent Antitumor Activity |
| title_fullStr | A Novel Anti-B7-H3 × Anti-CD3 Bispecific Antibody with Potent Antitumor Activity |
| title_full_unstemmed | A Novel Anti-B7-H3 × Anti-CD3 Bispecific Antibody with Potent Antitumor Activity |
| title_short | A Novel Anti-B7-H3 × Anti-CD3 Bispecific Antibody with Potent Antitumor Activity |
| title_sort | novel anti b7 h3 anti cd3 bispecific antibody with potent antitumor activity |
| topic | B7-H3 bispecific T cell engager solid tumor immunotherapy |
| url | https://www.mdpi.com/2075-1729/12/2/157 |
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