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

Molecular Therapy: Oncolytics

Lukas Flatz¹  Burkhard Ludewig¹  Erika Schmidt²  Michał Królik³  Omar Hasan Ali³  Sandra S. Ring³  Fabienne Hartmann³  Stefan Kochanek³ 

[1] Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland;Department of Gene Therapy, Ulm University, Helmholtzstrasse 8, 89081 Ulm, Germany;Institute of Immunobiology, Kantonsspital St.Gallen, Rorschacher Strasse 95, 9007 St.Gallen, Switzerland;

关键词: Cancer vaccination;    Viral Vectors;    Melanoma;    gp100;    heterologous prime boost;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown