He Xiangfeng, Wang Jing, Dou Jun, Yu Fangliu, Cai Kai, Li Xiaoli, Zhang Hongyi, Gu Ning
Department of Pathogenic Biology and Immunology, Medical School;
Exp Ther Med. 2011 Sep;2(5):911-916. doi: 10.3892/etm.2011.283. Epub 2011 Jun 14.
An apoptotic tumor cell serves as a potential potent trigger for the initiation of naturally occurring tumor immunity. In the present study, a B16F10 tumor cell vaccine treated with mitoxantrone (MIT) was developed, and its antitumor effect on mice was evaluated. The results indicated that the B16F10 tumor cell vaccine treated with MIT alone or in combination with reserpine (RP) and verapamil (VP) for 12 h triggered apoptosis, and that the expression of CD80, the MHC II class molecule, NKG2D and its ligand were significantly increased compared to the expression levels in the control group. The tumor vaccine immunogenicity was significantly enhanced in the vaccinated mice, resulting in augmented cytotoxicity of splenocytes and NK cells as well as the splenocyte proliferative response compared to the control group mice. Notably, the mice vaccinated with the B16F10 tumor cell vaccine treated with MIT, RP and VP did not generate tumors only after 60 days into the observation, but the mice also generated a powerful immune prophylactic efficiency against the B16F10 tumor cell challenge. These findings demonstrated the safety and efficacy of the B16F10 tumor cell vaccine treated with MIT alone or in combination with RP and VP in the murine model, and suggest that an apoptotic tumor cell vaccine modeled on naturally occurring tumor immune responses in vivo may provide a safe and immunogenic tumor vaccine for potential applications in humans.
凋亡的肿瘤细胞可作为引发天然肿瘤免疫的潜在强效触发因素。在本研究中，研发了一种用米托蒽醌（MIT）处理的B16F10肿瘤细胞疫苗，并评估了其对小鼠的抗肿瘤作用。结果表明，单独用MIT或与利血平（RP）和维拉帕米（VP）联合处理12小时的B16F10肿瘤细胞疫苗可触发细胞凋亡，与对照组相比，CD80、MHC II类分子、NKG2D及其配体的表达显著增加。与对照组小鼠相比，接种疫苗的小鼠体内肿瘤疫苗的免疫原性显著增强，导致脾细胞和NK细胞的细胞毒性增强以及脾细胞增殖反应增强。值得注意的是，用MIT、RP和VP处理的B16F10肿瘤细胞疫苗接种的小鼠在观察60天后才未产生肿瘤，而且这些小鼠还对B16F10肿瘤细胞攻击产生了强大的免疫预防效果。这些发现证明了单独用MIT或与RP和VP联合处理的B16F10肿瘤细胞疫苗在小鼠模型中的安全性和有效性，并表明基于体内天然肿瘤免疫反应构建的凋亡肿瘤细胞疫苗可能为人类潜在应用提供一种安全且具有免疫原性的肿瘤疫苗。
