Ring Sandra S, Królik Michał, Hartmann Fabienne, Schmidt Erika, Ali Omar Hasan, Ludewig Burkhard, Kochanek Stefan, Flatz Lukas
Institute of Immunobiology, Kantonsspital St.Gallen, Rorschacher Strasse 95, 9007 St.Gallen, Switzerland.
Department of Gene Therapy, Ulm University, Helmholtzstrasse 8, 89081 Ulm, Germany.
Mol Ther Oncolytics. 2020 Oct 10;19:179-187. doi: 10.1016/j.omto.2020.10.001. eCollection 2020 Dec 16.
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.
癌症疫苗接种旨在诱导针对肿瘤衍生抗原的适应性免疫反应。在本研究中，我们利用重组人5型腺病毒（rAd5）和基于重组淋巴细胞性脉络丛脑膜炎病毒（rLCMV）的载体来表达黑素细胞分化抗原gp100。与单次或同源疫苗接种不同，异源初免-加强疫苗接种，即先用rAd5-gp100进行初免，随后用rLCMV-gp100进行加强注射，可诱导产生高数量的多功能gp100特异性CD8 T细胞。我们的数据表明，最佳的T细胞诱导取决于疫苗接种的顺序和间隔。用rAd5-和rLCMV-gp100进行预防性初免-加强疫苗接种可保护小鼠免受B16.F10黑色素瘤的攻击。在治疗环境中，疫苗接种与低剂量环磷酰胺联合使用显示出协同效应，并显著延迟了肿瘤生长。我们的研究结果表明，异源病毒载体初免-加强免疫可在小鼠黑色素瘤模型中介导肿瘤控制。
