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Cancers 2019, 11(3), 368; https://doi.org/10.3390/cancers11030368 (registering DOI)

Effect of Multiple Vaccinations with Tumor Cell-Based Vaccine with Codon-Modified GM-CSF on Tumor Growth in a Mouse Model

1
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
2
Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan 33302, Taiwan
3
Department of Biomedical Sciences, Chang Gung University, No. 259, Wenhua 1st Road, Kwei-Shan District, Taoyuan 33302, Taiwan
4
Division of Head & Neck Surgery, Department of Otolaryngology, Chang Gung Memorial Hospital, 5 Fushing Street, Kwei-Shan, Taoyuan 33302, Taiwan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 18 January 2019 / Revised: 7 March 2019 / Accepted: 11 March 2019 / Published: 15 March 2019
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Abstract

Ectopic expression of codon-modified granulocyte-macrophage colony-stimulating factor (cGM-CSF) in TC-1 cells (TC-1/cGM-CSF), a model cell line for human papillomavirus (HPV)-infected cervical cancer cells, increased the expression level of GM-CSF and improved the efficacy of tumor cell-based vaccines in a cervical cancer mouse model. The number of vaccine doses required to induce a long-term immune response in a cervical cancer mouse model is poorly understood. Here, we investigated one, three, and five doses of the irradiated TC-1/cGM-CSF vaccine to determine which dose was effective in inducing a greater immune response and the suppression of tumors. Our findings showed that three doses of irradiated TC-1/cGM-CSF vaccine elicited slower tumor growth rates and enhanced survival rates compared with one dose or five doses of irradiated TC-1/cGM-CSF vaccine. Consistently, mice vaccinated with three doses of irradiated TC-1/cGM-CSF vaccine exhibited stronger interferon gamma (IFN-γ) production in HPV E7-specific CD8+ T cells and CD4+ T cells. A higher percentage of natural killer cells and interferon-producing killer dendritic cells (IKDCs) appeared in the splenocytes of the mice vaccinated with three doses of irradiated TC-1/cGM-CSF vaccine compared with those of the mice vaccinated with one dose or five doses of irradiated TC-1/cGM-CSF vaccine. Our findings demonstrate that single or multiple vaccinations, such as five doses, with irradiated TC-1/cGM-CSF vaccine suppressed the immune response, whereas three doses of irradiated TC-1/cGM-CSF vaccine elicited a greater immune response and subsequent tumor suppression. View Full-Text
Keywords: HPV; cGM-CSF; cervical cancer; multiple vaccinations; IKDCs HPV; cGM-CSF; cervical cancer; multiple vaccinations; IKDCs
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Qiu, J.T.; Alson, D.; Lee, T.-H.; Tsai, C.-C.; Yu, T.-W.; Chen, Y.-S.; Cheng, Y.-F.; Lin, C.-C.; Schuyler, S.C. Effect of Multiple Vaccinations with Tumor Cell-Based Vaccine with Codon-Modified GM-CSF on Tumor Growth in a Mouse Model. Cancers 2019, 11, 368.

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