Anti-VEGFR2-interferon-α2 regulates the tumor microenvironment and exhibits potent antitumor efficacy against colorectal cancer
Interferon-α (IFNα) has multiple antitumor effects including direct antitumor toxicity and the ability to potently stimulate both innate and adaptive immunity. However, its clinical applications in the treatment of malignancies have been limited because of short half-life and serious adverse reactio...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-03-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2017.1290038 |
| _version_ | 1818495043394076672 |
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| author | Zhaoting Li Yijia Zhu Chenchen Li Ryan Trinh Xueyan Ren Fumou Sun Youfu Wang Pengzhao Shang Tong Wang Min Wang Sherie L. Morrison Juan Zhang |
| author_facet | Zhaoting Li Yijia Zhu Chenchen Li Ryan Trinh Xueyan Ren Fumou Sun Youfu Wang Pengzhao Shang Tong Wang Min Wang Sherie L. Morrison Juan Zhang |
| author_sort | Zhaoting Li |
| collection | DOAJ |
| description | Interferon-α (IFNα) has multiple antitumor effects including direct antitumor toxicity and the ability to potently stimulate both innate and adaptive immunity. However, its clinical applications in the treatment of malignancies have been limited because of short half-life and serious adverse reactions when attempting to deliver therapeutically effective doses. To address these issues, we fused IFNα2a to the anti-vascular endothelial growth factor and receptor 2 (VEGFR2) antibody JZA00 with the goal of targeting it to the tumor microenvironment where it can stimulate the antitumor immune response. The fusion protein, JZA01, is effective against colorectal cancer by inhibiting angiogenesis, exhibiting direct cytotoxicity, and activating the antitumor immune response. Although JZA01 exhibited reduced IFNα2 activity in vitro compared with native IFNα2, VEGFR2 targeting permitted efficient antiproliferative, proapoptotic, antiangiogenesis, and immune-stimulating effects against the colorectal tumors HCT-116 and SW620. JZA01 showed in vivo efficacy in NOD-SCID mice-bearing established HCT-116 tumors. In conclusion, this study describes an antitumor immunotherapy that is highly promising for the treatment of colorectal cancer. |
| first_indexed | 2024-12-10T18:15:01Z |
| format | Article |
| id | doaj.art-26b836d0df534732829acde3a9465f0d |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-10T18:15:01Z |
| publishDate | 2017-03-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-26b836d0df534732829acde3a9465f0d2022-12-22T01:38:21ZengTaylor & Francis GroupOncoImmunology2162-402X2017-03-016310.1080/2162402X.2017.12900381290038Anti-VEGFR2-interferon-α2 regulates the tumor microenvironment and exhibits potent antitumor efficacy against colorectal cancerZhaoting Li0Yijia Zhu1Chenchen Li2Ryan Trinh3Xueyan Ren4Fumou Sun5Youfu Wang6Pengzhao Shang7Tong Wang8Min Wang9Sherie L. Morrison10Juan Zhang11State Key Laboratory of Natural Medicines, China Pharmaceutical UniversityState Key Laboratory of Natural Medicines, China Pharmaceutical UniversityState Key Laboratory of Natural Medicines, China Pharmaceutical UniversityUniversity of California Los AngelesState Key Laboratory of Natural Medicines, China Pharmaceutical UniversityState Key Laboratory of Natural Medicines, China Pharmaceutical UniversityState Key Laboratory of Natural Medicines, China Pharmaceutical UniversityState Key Laboratory of Natural Medicines, China Pharmaceutical UniversityState Key Laboratory of Natural Medicines, China Pharmaceutical UniversityState Key Laboratory of Natural Medicines, China Pharmaceutical UniversityUniversity of California Los AngelesState Key Laboratory of Natural Medicines, China Pharmaceutical UniversityInterferon-α (IFNα) has multiple antitumor effects including direct antitumor toxicity and the ability to potently stimulate both innate and adaptive immunity. However, its clinical applications in the treatment of malignancies have been limited because of short half-life and serious adverse reactions when attempting to deliver therapeutically effective doses. To address these issues, we fused IFNα2a to the anti-vascular endothelial growth factor and receptor 2 (VEGFR2) antibody JZA00 with the goal of targeting it to the tumor microenvironment where it can stimulate the antitumor immune response. The fusion protein, JZA01, is effective against colorectal cancer by inhibiting angiogenesis, exhibiting direct cytotoxicity, and activating the antitumor immune response. Although JZA01 exhibited reduced IFNα2 activity in vitro compared with native IFNα2, VEGFR2 targeting permitted efficient antiproliferative, proapoptotic, antiangiogenesis, and immune-stimulating effects against the colorectal tumors HCT-116 and SW620. JZA01 showed in vivo efficacy in NOD-SCID mice-bearing established HCT-116 tumors. In conclusion, this study describes an antitumor immunotherapy that is highly promising for the treatment of colorectal cancer.http://dx.doi.org/10.1080/2162402X.2017.1290038cd8+ t cellscolorectal cancerdcsifnα2tumor microenvironmentvegfr2 |
| spellingShingle | Zhaoting Li Yijia Zhu Chenchen Li Ryan Trinh Xueyan Ren Fumou Sun Youfu Wang Pengzhao Shang Tong Wang Min Wang Sherie L. Morrison Juan Zhang Anti-VEGFR2-interferon-α2 regulates the tumor microenvironment and exhibits potent antitumor efficacy against colorectal cancer OncoImmunology cd8+ t cells colorectal cancer dcs ifnα2 tumor microenvironment vegfr2 |
| title | Anti-VEGFR2-interferon-α2 regulates the tumor microenvironment and exhibits potent antitumor efficacy against colorectal cancer |
| title_full | Anti-VEGFR2-interferon-α2 regulates the tumor microenvironment and exhibits potent antitumor efficacy against colorectal cancer |
| title_fullStr | Anti-VEGFR2-interferon-α2 regulates the tumor microenvironment and exhibits potent antitumor efficacy against colorectal cancer |
| title_full_unstemmed | Anti-VEGFR2-interferon-α2 regulates the tumor microenvironment and exhibits potent antitumor efficacy against colorectal cancer |
| title_short | Anti-VEGFR2-interferon-α2 regulates the tumor microenvironment and exhibits potent antitumor efficacy against colorectal cancer |
| title_sort | anti vegfr2 interferon α2 regulates the tumor microenvironment and exhibits potent antitumor efficacy against colorectal cancer |
| topic | cd8+ t cells colorectal cancer dcs ifnα2 tumor microenvironment vegfr2 |
| url | http://dx.doi.org/10.1080/2162402X.2017.1290038 |
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