Heterologous Prime Boost Vaccination Induces Protective Melanoma-Specific CD8+ T Cell Responses

Sandra S Ring; Michał Królik; Fabienne Hartmann; Erika Schmidt; Omar Hasan Ali; Burkhard Ludewig; Stefan Kochanek; Lukas Flatz

doi:10.1016/j.omto.2020.10.001

Heterologous Prime Boost Vaccination Induces Protective Melanoma-Specific CD8⁺ T Cell Responses

Mol Ther Oncolytics. 2020 Oct 10:19:179-187. doi: 10.1016/j.omto.2020.10.001. eCollection 2020 Dec 16.

Authors

Sandra S Ring¹, Michał Królik¹, Fabienne Hartmann¹, Erika Schmidt², Omar Hasan Ali^{1

3}, Burkhard Ludewig^{1

3}, Stefan Kochanek², Lukas Flatz^{1

4

5

6}

Affiliations

¹ Institute of Immunobiology, Kantonsspital St.Gallen, Rorschacher Strasse 95, 9007 St.Gallen, Switzerland.
² Department of Gene Therapy, Ulm University, Helmholtzstrasse 8, 89081 Ulm, Germany.
³ Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
⁴ Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland.
⁵ Department of Oncology and Hematology, Kantonsspital St.Gallen, Rorschacher Strasse 95, 9007 St.Gallen, Switzerland.
⁶ Department of Dermatology, Kantonsspital St.Gallen, Rorschacher Strasse 95, 9007 St.Gallen, Switzerland.

Abstract

Cancer vaccination aims at inducing an adaptive immune response against tumor-derived antigens. In this study, we utilize recombinant human adenovirus serotype 5 (rAd5) and recombinant lymphocytic choriomeningitis virus (rLCMV)-based vectors expressing the melanocyte differentiation antigen gp100. In contrast to single or homologous vaccination, a heterologous prime boost vaccination starting with a rAd5-gp100 prime immunization followed by a rLCMV-gp100 boost injection induces a high magnitude of polyfunctional gp100-specific CD8⁺ T cells. Our data indicate that an optimal T cell induction is dependent on the order and interval of the vaccinations. A prophylactic prime boost vaccination with rAd5- and rLCMV-gp100 protects mice from a B16.F10 melanoma challenge. In the therapeutic setting, combination of the vaccination with low-dose cyclophosphamide showed a synergistic effect and significantly delayed tumor growth. Our findings suggest that heterologous viral vector prime boost immunizations can mediate tumor control in a mouse melanoma model.

Keywords: Cancer vaccination; Melanoma; Viral Vectors; gp100; heterologous prime boost.