Effect of multiple vaccinations with tumor cell-based vaccine with codon-modified GM-CSF on tumor growth in a mouse model

Jiantai Timothy Qiu, Donia Alson, Ta Hsien Lee, Ching Chou Tsai, Ting Wei Yu, Yu Sing Chen, Ya Fang Cheng, Chu Chi Lin, Scott C. Schuyler

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

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-) 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.

Original languageEnglish
Article number368
JournalCancers
Volume11
Issue number3
DOIs
Publication statusPublished - Mar 2019
Externally publishedYes

Keywords

  • Cervical cancer
  • CGM-CSF
  • HPV
  • IKDCs
  • Multiple vaccinations

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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