Naked RNA vaccine controls tumors with down-regulated MHC class I expression through NK cells and perforin-dependent pathways

Wen Fang Cheng, Chien Fu Hung, Chien Nan Lee, Yi Ning Su, Ming Cheng Chang, Liangmei He, T. C. Wu, Chi An Chen, Chang Yao Hsieh

Research output: Contribution to journalArticle

Abstract

One of the major issues facing cancer immunotherapy is that many human cancers down-regulate expression of MHC class I molecules. The understanding of the mechanisms of antitumor effects against tumors with down-regulated MHC class I will facilitate rational design of vaccines and immunotherapeutic strategies to control such tumors. A naked Sind-bis RNA replicon vector (SINrep5) encoding the herpes simplex virus type 1 protein VP22 linked to E7 (SINrep5-VP22/E7) generated significant antitumor effects against TC-1 and TC-1 P3(A15), tumors with down-regulated MHC class I expression. Naked SINrep5 RNA without the insert or an E7 vaccine also produced antitumor effects against TC-1 P3(A15) but not TC-1. Mice vaccinated with any of these naked RNA vaccines generated higher percentages of NK cells. In vivo Ab depletion experiments revealed that NK cells were important for the antitumor effects of naked RNA vaccines against TC-1 P3(A15) and that the antitumor effects were perforin-dependent. Poly I:C also increased the percentage of NK cells and generated antitumor effects against the tumors with down-regulated MHC class I. Thus, the SINrep5-VP22/E7 naked RNA vaccine controls MHC class I-positive and MHC class I-down-regulated tumor cells via different mechanisms, and NK cells play an important role in the antitumor effects generated by naked RNA replicon vaccines.

Original languageEnglish (US)
Pages (from-to)1892-1900
Number of pages9
JournalEuropean Journal of Immunology
Volume34
Issue number7
DOIs
StatePublished - Jul 1 2004

Keywords

  • HPV
  • NK cells
  • Naked RNA replicon vaccine
  • Tumor evasion
  • Tumor with down-regulated MHC class I expression

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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