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* Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5535, Université Montpellier 1 and 2, Montpellier, France;
Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain; and
Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Institut National du Cancer/Cancéropôle Grand Sud-Ouest (to M.V.), La Ligue Nationale Contre le Cancer: Comité de la Lozère (to M.V.), the Association pour la Recherche sur le Cancer (to R.A.H.), the Spanish Ministerio de Educación Grant SAF2007-65144 (to A.A.), as well as by fellowships from La Ligue Nationale Contre le Cancer: Comité Nationale (to J.G.), the Région Languedoc-Rousillon (to S.C.), and a Formación de Personal Investigador fellowship associated with Grant SAF2004-03058 from the the Ministerio de Educación y Ciencia/Fondo Social Europeo (to J.I.A.). This research was also supported in part by the Intramural Research Program of the National Institutes of Health National Cancer Institute, Center for Cancer Research.
2 S.C., J.I.A., and J.G. contributed equally to this paper.
3 Address correspondence and reprint requests to Dr. Martin Villalba, Institut de Génétique Moléculaire de Montpellier, 1919 route de Mende, 34293 Montpellier cedex 5, France; E-mail address: martin.villalba{at}igmm.cnrs.fr
4 Abbreviations used in this paper: DC, dendritic cell; β2-m, β2-microglobulin; MHC-I, MHC class I; sh, small hairpin; wt, wild type.
5 The online version of this article contains supplemental material.
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