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RESEARCH PRODUCT
Cytomegalovirus vector expressing RAE-1γ induces enhanced anti-tumor capacity of murine CD8+ T cells
Astrid KrmpotićTihana TršanKilian SchoberDirk H. BuschStipan JonjićNiels A. W. LemmermannWilliam J. BrittMartin MesserlePetra FilipovićKristina VukovićAna Lesac Brizićsubject
0301 basic medicineTumor vaccine [RAE-1γ]medicine.medical_treatmentT cellImmunologyGenetic VectorsProgrammed Cell Death 1 ReceptorMelanoma ExperimentalCytomegalovirusEpitopes T-LymphocyteBiologyCD8-Positive T-LymphocytesCancer VaccinesArticleCMV vectorNKG2DImmunomodulation03 medical and health sciencesMiceImmune systemTIGITKLRG1+ CD8+ T cellsNeoplasmsmedicineImmunology and AllergyCytotoxic T cellAnimalsHumansRAE-1γ : Tumor vaccineLectins C-TypeReceptors ImmunologicαTIGIT ; CMV vector ; KLRG1+ CD8+ T cells ; NKG2D ; RAE-1γ : Tumor vaccineBIOMEDICINE AND HEALTHCARE. Basic Medical Sciences.Membrane ProteinsImmunotherapyNKG2DVirology3. Good healthKiller Cells NaturalDisease Models Animal030104 developmental biologymedicine.anatomical_structureImmunizationAnimals NewbornFemaleαTIGITImmunotherapyBIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti.CD8description
Designing of CD8 T cell vaccines which would provide protection against tumors is still considered a great challenge in immunotherapy. Here we show a robust potential of a 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. Expression of RAE-1γ by the CMV vector 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-07-04 |