Tumor cell-based vaccines are currently used in clinical trails, but they are in general poorly immunogenic because they are composed of cell extracts or apoptotic cells. Live tumor cells should be much better Ags provided that they are properly processed by the host immune system. We show herein that stable expression of a small hairpin RNA for ERK5 (shERK5) decreases ERK5 levels in human and mouse leukemic cells and leads to their elimination by NK cells in vivo. The shERK5 cells show down-regulation of MHC class I expression at the plasma membrane. Accordingly, ectopic activation of the ERK5 pathway induces MHC class I gene expression. Coinjection of shERK5-expressing cells into the peritoneum diminishes survival of engrafted wild-type tumor cells. Moreover, s.c. injection of shERK5-expressing cells strongly diminishes tumor development by wild-type cells. Our results show that shERK5 expression in leukemia cells effectively attenuates their tumor activity and allows their use as a tumor cell-based vaccine.
ERK5 knockdown generates mouse leukemia cells with low MHC class I levels that activate NK cells and block tumorigenesis
Charni, S.; Aguilo, J. I.; Garaude, J.; de Bettignies, G.; Jacquet, C.; Hipskind, R. A.; Singer, D.; Anel, A.; Villalba, M.
2009-03-15 / vol 182 / pages 3398-405
182/6/3398 [pii] 10.4049/jimmunol.0803006
1550-6606 (Electronic) 0022-1767 (Linking)
Cell Line, Tumor; Humans; Animals; Cells, Cultured; Mice; Mice, Inbred C57BL; Mice, Inbred BALB C; Killer Cells, Natural/*immunology/metabolism; Lymphocyte Activation/*immunology; Jurkat Cells; *Gene Knockdown Techniques; Cancer Vaccines/administration & dosage/genetics/*immunology; Cytotoxicity, Immunologic/genetics; Histocompatibility Antigens Class I/biosynthesis/genetics/*metabolism; inhibitors/biosynthesis/*genetics; Leukemia L1210/enzymology/genetics/immunology/*prevention & control; Mitogen-Activated Protein Kinase 7/*antagonists &; RNA, Small Interfering/physiology; Signal Transduction/genetics/immunology