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

Molecular Therapy: Oncolytics (Dec 2020)

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

Affiliations

Sandra S. Ring: Institute of Immunobiology, Kantonsspital St.Gallen, Rorschacher Strasse 95, 9007 St.Gallen, Switzerland
Michał Królik: Institute of Immunobiology, Kantonsspital St.Gallen, Rorschacher Strasse 95, 9007 St.Gallen, Switzerland
Fabienne Hartmann: Institute of Immunobiology, Kantonsspital St.Gallen, Rorschacher Strasse 95, 9007 St.Gallen, Switzerland
Erika Schmidt: Department of Gene Therapy, Ulm University, Helmholtzstrasse 8, 89081 Ulm, Germany
Omar Hasan Ali: Institute of Immunobiology, Kantonsspital St.Gallen, Rorschacher Strasse 95, 9007 St.Gallen, Switzerland; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland
Burkhard Ludewig: Institute of Immunobiology, Kantonsspital St.Gallen, Rorschacher Strasse 95, 9007 St.Gallen, Switzerland; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland
Stefan Kochanek: Department of Gene Therapy, Ulm University, Helmholtzstrasse 8, 89081 Ulm, Germany
Lukas Flatz: Institute of Immunobiology, Kantonsspital St.Gallen, Rorschacher Strasse 95, 9007 St.Gallen, Switzerland; Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland; Department of Oncology and Hematology, Kantonsspital St.Gallen, Rorschacher Strasse 95, 9007 St.Gallen, Switzerland; Department of Dermatology, Kantonsspital St.Gallen, Rorschacher Strasse 95, 9007 St.Gallen, Switzerland; Corresponding author: Lukas Flatz, MD, Institute of Immunobiology, Kantonsspital St. Gallen, Rorschacher Strasse 95, 9007 St. Gallen, Switzerland.

Journal volume & issue: Vol. 19
pp. 179 – 187

Abstract

Read online

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.

Published in Molecular Therapy: Oncolytics

ISSN: 2372-7705 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.cell.com/molecular-therapy-family/oncolytics/latest-content

About the journal

Abstract

Keywords