CD8+ T cells, NK cells and IFN-γ are important for control of tumor with downregulated MHC class I expression by DNA vaccination

W. F. Cheng, C. F. Hung, K. Y. Lin, M. Ling, J. Juang, L. He, C. T. Lin, T. C. Wu

Research output: Contribution to journalReview articlepeer-review

50 Scopus citations

Abstract

One of the major hurdles facing cancer immunotherapy is that cancers may downregulate expression of MHC class I molecules. The development of a suitable tumor model with downregulated MHC class I expression is critical for designing vaccines and immunotherapeutic strategies to control such tumors. We developed an E7-expressing murine tumor model with downregulated MHC class I expression, TC-1 P3 (A15). Using this model, we tested DNA and vaccinia vaccines for their ability to control tumors with downregulated MHC class I expression. We found that vaccination with DNA encoding E7 linked to Mycobacterial heat shock protein 70 (HSP70) generated a significant antitumor effect against TC-1 P3 (A15), while vaccination with E7/HSP70 vaccinia did not generate an appreciable antitumor effect. Lymphocyte depletion experiments revealed that both-CD8+ T cells and NK cells were essential for the antitumor effect generated by E7/HSP70 DNA against TC-1 P3 (A 15). Furthermore, tumor protection experiments using IFN-γ knockout mice revealed that IFN-γ was essential for the antitumor effect generated by E7/HSP70 DNA against TC-1 P3 (A 15). Our results demonstrate that vaccination with E7/HSP70 DNA results in a significant antitumor effect against a neoplasm with downregulated MHC class I expression and the importance of CD8+ T cells, NK cells, and IFN-γ in generating this antitumor effect.

Original languageEnglish (US)
Pages (from-to)1311-1320
Number of pages10
JournalGene Therapy
Volume10
Issue number16
DOIs
StatePublished - Aug 2003

Keywords

  • Cancer immunotherapy
  • DNA vaccine
  • HPV
  • Immune evasion

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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