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

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.

• Authors: Tihana Tršan, Kristina Vuković, Petra Filipović, Ana Lesac Brizić, Niels A W Lemmermann, Kilian Schober, Dirk H Busch, William J Britt, Martin Messerle, Astrid Krmpotić, Stipan Jonjić
• Journal: European journal of immunology (Eur J Immunol) Vol. 47 Issue 8 Pg. 1354-1367 (08 2017) ISSN: 1521-4141 [Electronic] Germany
• PMID: 28612942 (Publication Type: Journal Article)
• Copyright: © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Cancer Vaccines
• Epitopes, T-Lymphocyte
• Klrg1 protein, mouse
• Lectins, C-Type
• Membrane Proteins
• Pdcd1 protein, mouse
• Programmed Cell Death 1 Receptor
• Raet1c protein, mouse
• Receptors, Immunologic
• T cell Ig and ITIM domain protein, mouse

Topics

• Animals
• Animals, Newborn
• CD8-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (immunology)
• Cytomegalovirus (genetics, immunology)
• Disease Models, Animal
• Epitopes, T-Lymphocyte (immunology)
• Female
• Genetic Vectors
• Humans
• Immunomodulation
• Immunotherapy (methods)
• Killer Cells, Natural (immunology)
• Lectins, C-Type
• Melanoma, Experimental (immunology, therapy)
• Membrane Proteins (genetics, immunology)
• Mice
• Neoplasms (immunology, prevention & control, therapy)
• Programmed Cell Death 1 Receptor (antagonists & inhibitors, immunology)
• Receptors, Immunologic (antagonists & inhibitors, genetics, immunology)