[关键词]
[摘要]
在发生凋亡和受到信号刺激时,细胞会释放直径为0.1~1 μm的膜状囊泡,这样的膜状囊泡称之为微颗粒。其释放受到细胞骨架和生物机械力的影响,在正常细胞和恶性肿瘤细胞中起着传递信息的作用。最近笔者实验室通过肿瘤细胞来源的囊泡研发出一套新型的天然载药系统,其可以有效地将药物输送到肿瘤干细胞的细胞核,进而有效杀伤肿瘤干细胞而不产生副作用。其潜在的机制涉及肿瘤干细胞的柔软特性可以更好地摄取囊泡,载药囊泡进入溶酶体并促进溶酶体向细胞核运动进而将药物输送至细胞核。肿瘤细胞来源的载药囊泡已经进入临床试验,用于治疗梗阻性肿瘤和肿瘤导致的恶性积液。此外,肿瘤细胞来源的囊泡可以有效地被DC摄取,通过改变肿瘤细胞溶酶体的pH值以及激活DC的cGAS/STING通路产生Ⅰ型干扰素,进而促进DC对肿瘤细胞的抗原提呈,因而肿瘤细胞来源的囊泡可以作为理想的抗肿瘤疫苗。总之,肿瘤细胞来源的囊泡在今后的肿瘤免疫生物治疗和预防中有着广泛的应用前景。
[Key word]
[Abstract]
In recent years, the breakthroughs of targeting agents for tumor therapies and personalized molecular diagnosis have prompted cancer treatment into the era of precision medicine. However, established assessment for solid tumors treatment such as the WHO or RECIST evaluation criteria could not reflex precisely the efficacy of the targeted therapeutics and the survival benefits they provided to patients. Therefore, it is extremely urgent to explore and establish a new response assessment criteria for targeted tumor therapeutics. This article reviewed the history of the efficacy assessment criteria for anti-tumor drugs and current opinions on the subject. I also introduced the evolution and development of evaluation criteria for various targeted therapeutics toward different tumors, and focused on the new criteria for evaluating immuno-related therapeutics. Finally, I discussed in detail the proposed evaluation criteria, its definition, guiding principle and clinical application. It is conceivable that the continuous improvements in evaluating targeted therapeutics for solid tumors will bring transformation to personalized cancer treatment.
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[基金项目]
国家重点基础研究发展规划 (973 计划)资助项目 (No.2014CB542100);国家杰出青年基金资助项目(No.81225021);国家自然科学基金资助项目(No.81472653);中国卫生部公益事业专项基金资助项目(No.201302018)