Cytomegalovirus-Based Vaccine Expressing a Modified Tumor Antigen Induces Potent Tumor-Specific CD8+ T-cell Response and Protects Mice from Melanoma
Cytomegalovirus-Based Vaccine Expressing a Modified Tumor Antigen Induces Potent Tumor-Specific CD8+ T-cell Response and Protects Mice from Melanoma
复制标题
DOI：
10.1158/2326-6066.cir-14-0044
复制
发表时间：
2015-05-01
影响因子：
10.1
通讯作者：
Khanna, Kamal M.
中科院分区：
文献类型：
--
作者：
Qiu, Zhijuan;Huang, Huakang;Khanna, Kamal M.
肿瘤浸润性CD 8（+）T细胞的存在与肿瘤消退和更好的预后相关。巨细胞病毒（CMV）感染可激发强而持久的CD 8（+）T细胞应答，这使得CMV成为一种潜在的有希望的抗癌疫苗载体。在目前的研究中，我们使用重组小鼠巨细胞病毒（MCMV）株作为预防和治疗疫苗的侵略性B16肺转移性黑色素瘤模型。用表达MCMV的卵清蛋白（OVA）免疫诱导了有效的OVA特异性CD 8（+）z T细胞应答，并以抗原依赖性方式有效保护小鼠免受表达OVA的B16黑色素瘤的侵害。我们设计MCMV以表达修饰的B16黑素瘤抗原gp 100（MCMV-gp 100 KGP）。MCMV-gp 100 KGP免疫在克服自身抗原免疫耐受方面非常有效，即使在存在预先存在的抗CMV免疫的情况下，也能诱导强烈、持久的gp 100特异性CD 8（+）T细胞应答。此外，MCMV-gp 100 KGP预防性和治疗性疫苗接种均有效地保护小鼠免受高度侵袭性肺B16-F10黑色素瘤的侵害，并且这种保护作用是由gp 100特异性CD 8（+）T细胞介导的。我们表明，MCMV是一个上级疫苗载体相比，常用的水泡性口炎病毒载体。总的来说，我们的研究表明，CMV是一种有前途的疫苗载体，以预防和治疗肿瘤。(c)2015年AACR。
The presence of tumor-infiltrating CD8(+) T cells is associated with tumor regression and better prognosis. Cytomegalovirus (CMV) infection elicits a robust and long-lasting CD8(+) T-cell response, which makes CMV a potentially promising vaccine vector against cancer. In the current study, we used recombinant murine CMV (MCMV) strains as prophylactic and therapeutic vaccines in an aggressive B16 lung metastatic melanoma model. Immunization with MCMV-expressing ovalbumin (OVA) induced a potent OVA-specific CD8(+)z T-cell response and was effective in protecting mice from OVA-expressing B16 melanoma in an antigen-dependent manner. We engineered MCMV to express a modified B16 melanoma antigen gp100 (MCMV-gp100KGP). Immunization with MCMV-gp100KGP was highly effective in overcoming immune tolerance to self-antigen and induced a strong, long-lasting gp100-specific CD8(+) T-cell response even in the presence of preexisting anti-CMV immunity. Furthermore, both prophylactic and therapeutic vaccinations of mice with MCMV-gp100KGP effectively protected mice from highly aggressive lung B16-F10 melanoma, and the protection was mediated by gp100-specific CD8(+) T cells. We showed that MCMV is a superior vaccine vector compared with a commonly used vesicular stomatitis virus vector. Collectively, our studies demonstrate that CMV is a promising vaccine vector to prevent and treat tumors. (c) 2015 AACR.