Bispecific antibody targeting TGF-β and PD-L1 for synergistic cancer immunotherapy
The PD-1/PD-L1 signaling pathway plays a crucial role in cancer immune evasion, and the use of anti-PD-1/PD-L1 antibodies represents a significant milestone in cancer immunotherapy. However, the low response rate observed in unselected patients and the development of therapeutic resistance remain ma...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1196970/full |
| _version_ | 1797781002842537984 |
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| author | Tianye Li Tianye Li Xinrun Wang Xinrun Wang Mengke Niu Mingli Wang Mingli Wang Jianwei Zhou Jianwei Zhou Kongming Wu Ming Yi |
| author_facet | Tianye Li Tianye Li Xinrun Wang Xinrun Wang Mengke Niu Mingli Wang Mingli Wang Jianwei Zhou Jianwei Zhou Kongming Wu Ming Yi |
| author_sort | Tianye Li |
| collection | DOAJ |
| description | The PD-1/PD-L1 signaling pathway plays a crucial role in cancer immune evasion, and the use of anti-PD-1/PD-L1 antibodies represents a significant milestone in cancer immunotherapy. However, the low response rate observed in unselected patients and the development of therapeutic resistance remain major obstacles to their clinical application. Accumulating studies showed that overexpressed TGF-β is another immunosuppressive factor apart from traditional immune checkpoints. Actually, the effects of PD-1 and TGF-β pathways are independent and interactive, which work together contributing to the immune evasion of cancer cell. It has been verified that blocking TGF-β and PD-L1 simultaneously could enhance the efficacy of PD-L1 monoclonal antibody and overcome its treatment resistance. Based on the bispecific antibody or fusion protein technology, multiple bispecific and bifunctional antibodies have been developed. In the preclinical and clinical studies, these updated antibodies exhibited potent anti-tumor activity, superior to anti-PD-1/PD-L1 monotherapies. In the review, we summarized the advances of bispecific antibodies targeting TGF-β and PD-L1 in cancer immunotherapy. We believe these next-generation immune checkpoint inhibitors would substantially alter the cancer treatment paradigm, especially in anti-PD-1/PD-L1-resistant patients. |
| first_indexed | 2024-03-12T23:51:39Z |
| format | Article |
| id | doaj.art-d04590015efc4b8d8bbe12eff45590cc |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T23:51:39Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d04590015efc4b8d8bbe12eff45590cc2023-07-13T13:50:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-07-011410.3389/fimmu.2023.11969701196970Bispecific antibody targeting TGF-β and PD-L1 for synergistic cancer immunotherapyTianye Li0Tianye Li1Xinrun Wang2Xinrun Wang3Mengke Niu4Mingli Wang5Mingli Wang6Jianwei Zhou7Jianwei Zhou8Kongming Wu9Ming Yi10Department of Gynecology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaZhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, ChinaDepartment of Gynecology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaZhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, ChinaCancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Science, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Gynecology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaZhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, ChinaDepartment of Gynecology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaZhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, ChinaCancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Science, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, ChinaThe PD-1/PD-L1 signaling pathway plays a crucial role in cancer immune evasion, and the use of anti-PD-1/PD-L1 antibodies represents a significant milestone in cancer immunotherapy. However, the low response rate observed in unselected patients and the development of therapeutic resistance remain major obstacles to their clinical application. Accumulating studies showed that overexpressed TGF-β is another immunosuppressive factor apart from traditional immune checkpoints. Actually, the effects of PD-1 and TGF-β pathways are independent and interactive, which work together contributing to the immune evasion of cancer cell. It has been verified that blocking TGF-β and PD-L1 simultaneously could enhance the efficacy of PD-L1 monoclonal antibody and overcome its treatment resistance. Based on the bispecific antibody or fusion protein technology, multiple bispecific and bifunctional antibodies have been developed. In the preclinical and clinical studies, these updated antibodies exhibited potent anti-tumor activity, superior to anti-PD-1/PD-L1 monotherapies. In the review, we summarized the advances of bispecific antibodies targeting TGF-β and PD-L1 in cancer immunotherapy. We believe these next-generation immune checkpoint inhibitors would substantially alter the cancer treatment paradigm, especially in anti-PD-1/PD-L1-resistant patients.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1196970/fullcancer immunotherapyimmunotherapy resistanceimmune checkpoint inhibitorbispecific antibodyTGF-βPD-L1 |
| spellingShingle | Tianye Li Tianye Li Xinrun Wang Xinrun Wang Mengke Niu Mingli Wang Mingli Wang Jianwei Zhou Jianwei Zhou Kongming Wu Ming Yi Bispecific antibody targeting TGF-β and PD-L1 for synergistic cancer immunotherapy Frontiers in Immunology cancer immunotherapy immunotherapy resistance immune checkpoint inhibitor bispecific antibody TGF-β PD-L1 |
| title | Bispecific antibody targeting TGF-β and PD-L1 for synergistic cancer immunotherapy |
| title_full | Bispecific antibody targeting TGF-β and PD-L1 for synergistic cancer immunotherapy |
| title_fullStr | Bispecific antibody targeting TGF-β and PD-L1 for synergistic cancer immunotherapy |
| title_full_unstemmed | Bispecific antibody targeting TGF-β and PD-L1 for synergistic cancer immunotherapy |
| title_short | Bispecific antibody targeting TGF-β and PD-L1 for synergistic cancer immunotherapy |
| title_sort | bispecific antibody targeting tgf β and pd l1 for synergistic cancer immunotherapy |
| topic | cancer immunotherapy immunotherapy resistance immune checkpoint inhibitor bispecific antibody TGF-β PD-L1 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1196970/full |
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