放疗联合免疫治疗的抗肿瘤效果及机制研究.pptxVIP

放疗联合免疫治疗的抗肿瘤效果及机制研究;2013年肿瘤免疫治疗被Science评为生命科学研究领域的“Breakthrough”突破性进展。 ;临床试验正在开展，结果显示联合治疗效果很好。 ;4;5; It is designed to have dual anti-cancer mechanism: Targeting immune effects to tumor site, i.e. anti-EGFR mAb arm concentrates IL-10 to tumor microenvironment and IL-10 will specifically activate tumor resident CD8+ T cells locally Direct tumor suppression by its anti-EGFR mAb for EGFR dependent tumors Higher drug level can be achieved through targeted delivery to the tumor micro-environment in EGFR+ tumors with reduced systemic exposure (higher tumor/blood ratio) IL-10 could potentially reduce anti-EGFR side effects (skin rash) because of its anti-inflammatory effects and relative lower levels of EGFR in skin than EGFR+ tumors A series of experiments have been conducted to characterize the molecule and demonstrate its antitumor activity in tumor models;;8;B16-EGFR;治疗肿瘤的效果研究;50-75% mice had tumor regression in DF203 treatment group (4mg/kg);12;13;14;适当的放疗剂量与Erb-(IL10)2 1mg/kg联合产生更好的治疗效果;放疗后三天给予Erb-(IL10)2 ，治疗效果最佳，免疫反应的有效发生大概需要三天左右的时间，所以以上结果印证假设：放疗引起免疫反应后协同三代抗体。;放疗产生的远位效应;RT10Gy单独或与Erb-(IL10)2 联合治疗是否能产生远位效应？;RT10Gy与Erb-(IL10)2 联合治疗主要通过何种免疫细胞起作用？;RT10Gy与Erb-(IL10)2 联合治疗能增强CD8+T分泌IFN-γ;联合治疗引起对侧肿瘤的消退是否源于抗肿瘤免疫的激活，细胞到达对侧病灶？;图二;总结和展望：