Cytomegalovirus vector expressing RAE‐1γ induces enhanced anti‐tumor capacity of murine CD8+ T cells |
| |
| Authors: | Tihana Tr?an Kristina Vukovi? Petra Filipovi? Ana Lesac Brizi? Niels A W Lemmermann Kilian Schober Dirk H Busch William J Britt Martin Messerle Stipan Jonji? |
| |
| Institution: | 1. Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia;2. Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia;3. Institute for Virology, University Medical Center of the Johannes Gutenberg‐University Mainz, Mainz, Germany;4. Institute for Medical Microbiology, Immunology and Hygiene, Technische Universit?t München (TUM), Munich, Germany;5. DZIF—National Centre for Infection Research, Munich and Hannover, Germany;6. Department of Pediatrics, University of Alabama Birmingham, School of Medicine, Birmingham, Alabama, USA;7. Department of Virology, Hannover Medical School, Hannover, Germany;8. Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, CroatiaThese authors are joint senior authors. |
| |
| Abstract: | 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. |
| |
| Keywords: | α TIGIT CMV vector KLRG1+ CD8+ T cells NKG2D RAE‐1γ Tumor vaccine α PD‐1 |
|
|
