A Single-Chain Variable Fragment Antibody/Chemokine Fusion Protein Targeting Human Endoglin to Enhance the Anti-Tumor Activity of Cytokine-Induced Killer Cells.
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| Abstract |
Cytokine-induced killer cell immunotherapy is an ideal candidate for adoptive cell transfer therapy. However, therapeutic approaches to enhance the anti-tumor activity of cytokine-induced killer cells remain to be explored. Here, we described the successful development of a novel antibody-chemokine fusion protein containing the anti-human Endoglin antibody in the single-chain variable fragment format and human interferon-gamma-induced protein 10 (hENG scFv/hIP-10). Its anti-Endoglin immunoreactivity and chemotactic activity against the cytokine-induced killer cells were characterized in vitro. To evaluate the anti-tumor effect in vivo, cytokine-induced killer cells were intravenously injected into human hepatocellular carcinoma-bearing nude mice, together with intratumoral administration of the fusion protein hENG scFv/hIP-10 as an enhancer. The tumor volume and survival time of the mice were monitored, whilst the tumor-infiltrating cytokine-induced killer cells, serum levels of interferon-gamma, tumor cell proliferation, apoptosis, and angiogenesis were measured. The results demonstrated that hENG scFv/hIP-10 and cytokine-induced killer cells synergistically inhibited tumor growth and prolonged survival of tumor-bearing mice. Moreover, the number of tumor-infiltrating cytokine-induced killer cells, serum levels of interferon-gamma, and tumor cell apoptosis were increased, accompanied with decreased tumor proliferation and angiogenesis. Thus, our study suggests that hENG scFv/hIP-10 could enhance the anti-tumor activity of cytokine-induced killer cells against human hepatocellular carcinoma.
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| Authors | Xuandong Lin, Haixia Li, Xi Li, Xiaomei Yang, Wei Shi, Ziqiang Ding, Dani Zhong, Yangzi Li, Wenli Yang, Xia Yu, Shenxia Xie, Xiaobing Jiang, Xiaoling Lu |
| Journal | Journal of biomedical nanotechnology (J Biomed Nanotechnol) Vol. 17 Issue 8 Pg. 1574-1583 (Aug 01 2021) ISSN: 1550-7033 [Print] United States |
| PMID | 34544535 (Publication Type: Journal Article) |
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