Smyth Mark J, Hayakawa Yoshihiro, Cretney Erika, Zerafa Nadeen, Sivakumar Pallavur, Yagita Hideo, Takeda Kazuyoshi
Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Center, A'Beckett Street, Victoria 8006, Australia.
J Immunol. 2006 May 15;176(10):6347-55. doi: 10.4049/jimmunol.176.10.6347.
Tumor cell apoptosis is the basis of many cancer therapies, and tumor-specific T cells are the principal effectors of successful anti-tumor immunotherapies. In this study, we show that induction of tumor cell apoptosis by agonistic mAb against DR5, combined with delayed IL-21 treatment, suppressed tumor growth and pre-established tumor metastases. Synergistic effects of the combination were observed in several tumor models where the target tumor was sensitive to DR5-mediated apoptosis. IL-21 promoted tumor-specific CTL activity and enhanced memory responses to tumor rechallenge. These results indicate that a rational combination of Ab-based therapy that causes tumor cell apoptosis and a cytokine that promotes T cell memory is a useful new strategy for cancer immunotherapy.
肿瘤细胞凋亡是许多癌症治疗的基础，而肿瘤特异性T细胞是成功的抗肿瘤免疫疗法的主要效应细胞。在本研究中，我们表明，抗DR5激动性单克隆抗体诱导肿瘤细胞凋亡并联合延迟给予白细胞介素-21治疗，可抑制肿瘤生长和已形成的肿瘤转移。在几种靶肿瘤对DR5介导的凋亡敏感的肿瘤模型中均观察到了联合治疗的协同效应。白细胞介素-21促进肿瘤特异性CTL活性，并增强对肿瘤再次攻击的记忆反应。这些结果表明，引发肿瘤细胞凋亡的基于抗体的疗法与促进T细胞记忆的细胞因子的合理联合是癌症免疫治疗的一种有用的新策略。
