Naslov
Cytomegalovirus vector expressing RAE-1γ induces enhanced anti-tumor capacity of murine CD8+ T cells

Autori
Tršan, Tihana ; Vuković, Kristina ; Filipović, Petra ; Lesac Brizić , Ana ; Lemmermann, N.A.W. ; Schober, K. ; Busch, D.H. ; Britt, .J. ; Messerle, M. ; Krmpotić, Astrid ; Jonjić, Stipan

Izvornik
European journal of immunology (0014-2980) 47 (2017), 8; 1354-1367

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
αTIGIT ; CMV vector ; KLRG1+ CD8+ T cells ; NKG2D ; RAE-1γ : Tumor vaccine

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA