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, Ken Yu Lin, M. Ling, J. Juang, L. He, C. T. Lin, T. C. Wu

Research output: Contribution to journalReview article

49 Citations (Scopus)

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 1 2003
Externally publishedYes

Fingerprint

Natural Killer Cells
Vaccination
Down-Regulation
HSP70 Heat-Shock Proteins
T-Lymphocytes
DNA
Neoplasms
Vaccinia
Lymphocyte Depletion
DNA Vaccines
Knockout Mice
Immunotherapy
Vaccines

Keywords

  • Cancer immunotherapy
  • DNA vaccine
  • HPV
  • Immune evasion

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

CD8+ T cells, NK cells and IFN-γ are important for control of tumor with downregulated MHC class I expression by DNA vaccination. / Cheng, W. F.; Hung, C. F.; Lin, Ken Yu; Ling, M.; Juang, J.; He, L.; Lin, C. T.; Wu, T. C.

In: Gene Therapy, Vol. 10, No. 16, 01.08.2003, p. 1311-1320.

Research output: Contribution to journalReview article

Cheng, W. F. ; Hung, C. F. ; Lin, Ken Yu ; Ling, M. ; Juang, J. ; He, L. ; Lin, C. T. ; Wu, T. C. / CD8+ T cells, NK cells and IFN-γ are important for control of tumor with downregulated MHC class I expression by DNA vaccination. In: Gene Therapy. 2003 ; Vol. 10, No. 16. pp. 1311-1320.
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