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

被引：4
|
作者：
Ring, Sandra S. [1 ]
Krolik, Michal [1 ]
Hartmann, Fabienne [1 ]
Schmidt, Erika [3 ]
Ali, Omar Hasan [1 ,2 ]
Ludewig, Burkhard [1 ,2 ]
Kochanek, Stefan [3 ]
Flatz, Lukas [1 ,4 ,5 ,6 ]
机构：
[1] Kantonsspital St Gallen, Inst Immunobiol, Rorschacher Str 95, CH-9007 St Gallen, Switzerland
[2] Univ Zurich, Inst Expt Immunol, Zurich, Switzerland
[3] Ulm Univ, Dept Gene Therapy, Helmholtzstr 8, D-89081 Ulm, Germany
[4] Univ Hosp Zurich, Dept Dermatol, Gloriastr 31, CH-8091 Zurich, Switzerland
[5] Kantonsspital St Gallen, Dept Oncol & Hematol, Rorschacher Str 95, CH-9007 St Gallen, Switzerland
[6] Kantonsspital St Gallen, Dept Dermatol, Rorschacher Str 95, CH-9007 St Gallen, Switzerland
来源：
MOLECULAR THERAPY-ONCOLYTICS | 2020年 / 19卷
关键词：
ANTIGEN-SPECIFIC CD8(+); METASTATIC MELANOMA; VIRAL VECTORS; VIRUS-INFECTION; DOUBLE-BLIND; CYCLOPHOSPHAMIDE; GENE; CANCER; IMMUNITY; INTERLEUKIN-2;
D O I：
10.1016/j.omto.2020.10.001
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
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.
引用
收藏
页码：179 / 187
页数：9
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