Naked RNA vaccine controls tumors with down-regulated MHC class I expression through NK cells and perforin-dependent pathways.
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 Sindbis 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.
Cheng
Wen-Fang
WF
Department of Obstetrics and Gynecology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan.
Hung
Chien-Fu
CF
Lee
Chien-Nan
CN
Su
Yi-Ning
YN
Chang
Ming-Cheng
MC
He
Liangmei
L
Wu
T-C
TC
Chen
Chi-An
CA
Hsieh
Chang-Yao
CY
D019264:Adoptive Transfer; D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D015536:Down-Regulation; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D008222:Lymphokines / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D054353:Perforin; D011070:Poly I-C / Q000494:pharmacology; D052899:Pore Forming Cytotoxic Proteins; D012313:RNA / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination
D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; D008222:Lymphokines; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D012313:RNA; D011070:Poly I-C