Cancer vaccine application is limited to specific cancer types because few cancer-associated antigens are known to induce tumor rejection. Accordingly, we assessed the utility of Ad881, an oncolytic adenovirus in which viral replication was strictly regulated by the cancer-specific midkine promoter, as a cancer vaccine in a murine colorectal cancer model lacking specific cancer-associated antigens. In CT26 and CMT93 cells, Ad881 (multiplicity of infection: 100 or 1,000) showed stronger cytotoxicity and oncolysis in vitro than its equivalent replication-defective adenovirus, Ad884. CT26 cells (1 × 104) infected with Ad881 (multiplicity of infection: 1,000) for 24 hours were suitable as vaccine antigens without tumor formation in our model. Repeated vaccinations, but not single vaccination, induced a greater prophylactic immune response. The percentage of mice that rejected the tumor challenge was 0, 4, and 38% after no vaccination, single vaccination, and repeated vaccinations, respectively. Immunogenic cell death marker high-mobility group box 1 protein (HMGB1) and adenosine triphosphate in culture medium were higher after Ad881 infection (24.3 ng/ml and 48.2 nmol/l, respectively) than after Ad884 infection (8.6 ng/ml and 15.4 nmol/l, respectively) or oxaliplatin treatment (3.7 ng/ml and 1.8 nmol/l, respectively). These results indicate that repeated whole cell vaccination using an oncolytic adenovirus may be a potent approach to evoke immunogenic cell death.

中文翻译：

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使用溶瘤腺病毒利用免疫原性细胞死亡进行全细胞疫苗接种对结直肠癌模型有效。

癌症疫苗的应用仅限于特定的癌症类型，因为已知很少有与癌症相关的抗原会诱导肿瘤排斥。因此，我们评估了Ad881（一种溶瘤腺病毒，其中病毒复制受到癌症特异性中期因子启动子的严格调控）作为缺乏特定癌症相关抗原的鼠结肠直肠癌模型的癌症疫苗的效用。在CT26和CMT93细胞中，Ad881（感染复数：100或1,000）在体外显示出比其同等复制缺陷型腺病毒Ad884更强的细胞毒性和溶瘤作用。在我们的模型中，用Ad881（感染复数：1,000）感染24小时的CT26细胞（1×104）适合作为没有肿瘤形成的疫苗抗原。重复接种疫苗，但未接种一次疫苗，可引发更大的预防性免疫反应。在未接种疫苗，单次接种疫苗和重复接种疫苗后，拒绝肿瘤攻击的小鼠百分比分别为0％，4％和38％。Ad881感染后（24.3 ng / ml和48.2 nmol / l）的培养基中的免疫原性细胞死亡标记物高迁移率族box 1蛋白（HMGB1）和三磷酸腺苷分别高于Ad884感染后的8.6 ng / ml和15.4 nmol / l）或奥沙利铂治疗（分别为3.7 ng / ml和1.8 nmol / l）。这些结果表明，使用溶瘤腺病毒重复进行全细胞疫苗接种可能是引起免疫原性细胞死亡的有效方法。Ad881感染后（24.3 ng / ml和48.2 nmol / l）的培养基中的免疫原性细胞死亡标记物高迁移率族box 1蛋白（HMGB1）和三磷酸腺苷分别高于Ad884感染后的8.6 ng / ml和15.4 nmol / l）或奥沙利铂治疗（分别为3.7 ng / ml和1.8 nmol / l）。这些结果表明，使用溶瘤腺病毒重复进行全细胞疫苗接种可能是引起免疫原性细胞死亡的有效方法。Ad881感染后（24.3 ng / ml和48.2 nmol / l）的培养基中的免疫原性细胞死亡标记物高迁移率族box 1蛋白（HMGB1）和三磷酸腺苷分别高于Ad884感染后的8.6 ng / ml和15.4 nmol / l）或奥沙利铂治疗（分别为3.7 ng / ml和1.8 nmol / l）。这些结果表明，使用溶瘤腺病毒重复进行全细胞疫苗接种可能是引起免疫原性细胞死亡的有效方法。