Intratumoral delivery of a novel oncolytic adenovirus encoding human antibody against PD-1 elicits enhanced antitumor efficacy
To date, diverse combination therapies with immune checkpoint inhibitors (ICIs), particularly oncolytic virotherapy, have demonstrated enhanced therapeutic outcomes in cancer treatment. However, high pre-existing immunity against the widely used adenovirus human serotype 5 (AdHu5) limits its extensi...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-06-01
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| Series: | Molecular Therapy: Oncolytics |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770522000596 |
| _version_ | 1818200280497389568 |
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| author | Ping Zhou Xuchen Wang Man Xing Xi Yang Mangteng Wu Hongyang Shi Caihong Zhu Xiang Wang Yingying Guo Shubing Tang Zhong Huang Dongming Zhou |
| author_facet | Ping Zhou Xuchen Wang Man Xing Xi Yang Mangteng Wu Hongyang Shi Caihong Zhu Xiang Wang Yingying Guo Shubing Tang Zhong Huang Dongming Zhou |
| author_sort | Ping Zhou |
| collection | DOAJ |
| description | To date, diverse combination therapies with immune checkpoint inhibitors (ICIs), particularly oncolytic virotherapy, have demonstrated enhanced therapeutic outcomes in cancer treatment. However, high pre-existing immunity against the widely used adenovirus human serotype 5 (AdHu5) limits its extensive clinical application. In this study, we constructed an innovative oncolytic virus (OV) based on a chimpanzee adenoviral vector with low seropositivity in the human population, named AdC68-spE1A-αPD-1, which endows the parental OV (AdC68-spE1A-ΔE3) with the ability to express full-length anti-human programmed cell death-1 monoclonal antibody (αPD-1). In vitro studies indicated that the AdC68-spE1A-αPD-1 retained parental oncolytic capacity, and αPD-1 was efficiently secreted from the infected tumor cells and bound exclusively to human PD-1 (hPD-1) protein. In vivo, intratumoral treatment with AdC68-spE1A-αPD-1 resulted in significant tumor suppression, prolonged overall survival, and enhanced systemic antitumor memory response in an hPD-1 knockin mouse tumor model. This strategy outperformed the unarmed OV and was comparable with combination therapy with intratumoral injection of AdC68-spE1A-ΔE3 and systemic administration of commercial αPD-1. In summary, AdC68-spE1A-αPD-1 is a cost-effective approach with potential clinical applications. |
| first_indexed | 2024-12-12T02:35:09Z |
| format | Article |
| id | doaj.art-bae19cbf9a0a4d349086e5ea94618f27 |
| institution | Directory Open Access Journal |
| issn | 2372-7705 |
| language | English |
| last_indexed | 2024-12-12T02:35:09Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncolytics |
| spelling | doaj.art-bae19cbf9a0a4d349086e5ea94618f272022-12-22T00:41:18ZengElsevierMolecular Therapy: Oncolytics2372-77052022-06-0125236248Intratumoral delivery of a novel oncolytic adenovirus encoding human antibody against PD-1 elicits enhanced antitumor efficacyPing Zhou0Xuchen Wang1Man Xing2Xi Yang3Mangteng Wu4Hongyang Shi5Caihong Zhu6Xiang Wang7Yingying Guo8Shubing Tang9Zhong Huang10Dongming Zhou11Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaInstitut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China; Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai 201508, ChinaInstitut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai 201508, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai 201508, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai 201508, ChinaDepartment of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai 201508, ChinaInstitut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China; Corresponding author Zhong Huang, PhD, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China; Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China; Corresponding author Dongming Zhou, MD, PhD, Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.To date, diverse combination therapies with immune checkpoint inhibitors (ICIs), particularly oncolytic virotherapy, have demonstrated enhanced therapeutic outcomes in cancer treatment. However, high pre-existing immunity against the widely used adenovirus human serotype 5 (AdHu5) limits its extensive clinical application. In this study, we constructed an innovative oncolytic virus (OV) based on a chimpanzee adenoviral vector with low seropositivity in the human population, named AdC68-spE1A-αPD-1, which endows the parental OV (AdC68-spE1A-ΔE3) with the ability to express full-length anti-human programmed cell death-1 monoclonal antibody (αPD-1). In vitro studies indicated that the AdC68-spE1A-αPD-1 retained parental oncolytic capacity, and αPD-1 was efficiently secreted from the infected tumor cells and bound exclusively to human PD-1 (hPD-1) protein. In vivo, intratumoral treatment with AdC68-spE1A-αPD-1 resulted in significant tumor suppression, prolonged overall survival, and enhanced systemic antitumor memory response in an hPD-1 knockin mouse tumor model. This strategy outperformed the unarmed OV and was comparable with combination therapy with intratumoral injection of AdC68-spE1A-ΔE3 and systemic administration of commercial αPD-1. In summary, AdC68-spE1A-αPD-1 is a cost-effective approach with potential clinical applications. http://www.sciencedirect.com/science/article/pii/S2372770522000596chimpanzee adenovirusoncolytic viruscheckpoint inhibitorsPD-1combination cancer therapyalternative |
| spellingShingle | Ping Zhou Xuchen Wang Man Xing Xi Yang Mangteng Wu Hongyang Shi Caihong Zhu Xiang Wang Yingying Guo Shubing Tang Zhong Huang Dongming Zhou Intratumoral delivery of a novel oncolytic adenovirus encoding human antibody against PD-1 elicits enhanced antitumor efficacy Molecular Therapy: Oncolytics chimpanzee adenovirus oncolytic virus checkpoint inhibitors PD-1 combination cancer therapy alternative |
| title | Intratumoral delivery of a novel oncolytic adenovirus encoding human antibody against PD-1 elicits enhanced antitumor efficacy |
| title_full | Intratumoral delivery of a novel oncolytic adenovirus encoding human antibody against PD-1 elicits enhanced antitumor efficacy |
| title_fullStr | Intratumoral delivery of a novel oncolytic adenovirus encoding human antibody against PD-1 elicits enhanced antitumor efficacy |
| title_full_unstemmed | Intratumoral delivery of a novel oncolytic adenovirus encoding human antibody against PD-1 elicits enhanced antitumor efficacy |
| title_short | Intratumoral delivery of a novel oncolytic adenovirus encoding human antibody against PD-1 elicits enhanced antitumor efficacy |
| title_sort | intratumoral delivery of a novel oncolytic adenovirus encoding human antibody against pd 1 elicits enhanced antitumor efficacy |
| topic | chimpanzee adenovirus oncolytic virus checkpoint inhibitors PD-1 combination cancer therapy alternative |
| url | http://www.sciencedirect.com/science/article/pii/S2372770522000596 |
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