Cytomegalovirus vector expressing RAE-1γ induces enhanced anti-tumor capacity of murine CD8+ T cells.
Designing CD8+ T-cell vaccines, which would provide protection against tumors is still considered a great challenge in immunotherapy. Here we show the robust potential of cytomegalovirus (CMV) vector expressing the NKG2D ligand RAE-1γ as CD8+ T cell-based vaccine against malignant tumors. Immunization with the CMV vector expressing RAE-1γ, delayed tumor growth or even provided complete protection against tumor challenge in both prophylactic and therapeutic settings. Moreover, a potent tumor control in mice vaccinated with this vector can be further enhanced by blocking the immune checkpoints TIGIT and PD-1. CMV vector expressing RAE-1γ potentiated expansion of KLRG1+ CD8+ T cells with enhanced effector properties. This vaccination was even more efficient in neonatal mice, resulting in the expansion and long-term maintenance of epitope-specific CD8+ T cells conferring robust resistance against tumor challenge. Our data show that immunomodulation of CD8+ T-cell responses promoted by herpesvirus expressing a ligand for NKG2D receptor can provide a powerful platform for the prevention and treatment of CD8+ T-cell sensitive tumors.
['Tršan|Tihana|T|', 'Vuković|Kristina|K|', 'Filipović|Petra|P|', 'Brizić|Ana Lesac|AL|', 'Lemmermann|Niels A W|NAW|', 'Schober|Kilian|K|', 'Busch|Dirk H|DH|0000-0001-8713-093X', 'Britt|William J|WJ|', 'Messerle|Martin|M|', 'Krmpotić|Astrid|A|', 'Jonjić|Stipan|S|0000-0001-5003-3108']
D000818:Animals D000831:Animals, Newborn D018414:CD8-Positive T-Lymphocytes D019496:Cancer Vaccines D003587:Cytomegalovirus D004195:Disease Models, Animal D018984:Epitopes, T-Lymphocyte D005260:Female D005822:Genetic Vectors D006801:Humans D056747:Immunomodulation D007167:Immunotherapy D007694:Killer Cells, Natural D037181:Lectins, C-Type D008546:Melanoma, Experimental D008565:Membrane Proteins D051379:Mice D009369:Neoplasms D061026:Programmed Cell Death 1 Receptor D011971:Receptors, Immunologic
RAE-1γ NKG2D CMV vector KLRG1+ CD8+ T cells Tumor vaccine αPD-1 αTIGIT