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| 1 | 肿瘤免疫与基因治疗研究进展显示文摘随着新兴免疫检查点抑制剂、溶瘤病毒和嵌合抗原受体T(chimeric antigen receptor T, CAR-T)细胞等肿瘤免疫与基因治疗制品获批临床使用,肿瘤免疫与基因治疗已经改变了实体瘤、血液肿瘤的治疗现状,在全球范围内获得权威组织、专家的广泛共识,正在成为多种肿瘤的一线治疗方案.但是,该领域目前仍然面临免疫治疗相关不良反应较多、溶瘤病毒疗效不显著的问题,而CAR-T细胞治疗有待突破实体瘤治疗的瓶颈以及下调高昂的价格等.针对这些关键科学问题,四川大学华西医院从疾病分子网络研究到创新生物技术药物研发及转化进行了一系列探索,取得了较为丰硕的成果.本文对近年来其中有关肿瘤免疫与基因治疗的研究进行综述.期待华西医院以建院130周年为契机,未来持续产出更多世界一流的成果,引领学科发展,同时造福社会. | 何治尧 罗敏 杨莉 邓洪新 魏于全 | 2022 | 中国科学:生命科学2022，52，11： | 1 |
| 2 | Engineering prodrug nanomicelles as pyroptosis inducer for codelivery of PI3K/mTOR and CDK inhibitors to enhance antitumor immunity显示文摘Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response.However,single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways.The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications.To circumvent this issue,we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle(PNM)for cancer therapy.PNM was engineered by integrating the PI3K/m TOR inhibitor PF-04691502(PF)and the broad spectrum CDK inhibitor flavopiridol(Flav)into a single nanoplatform,which showed tumor-specific accumulation,activation and deep penetration in response to the high glutathione(GSH)tumoral microenvironment.The codelivery of PF and Flav could trigger gasdermin E(GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response.Furthermore,the combination of PNM-induced immunogenic pyroptosis with antiprogrammed cell death-1(a PD-1)immunotherapy further boosted the antitumor effect and prolonged the survival time of mice.Collectively,these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/m TOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy. | Qichao Yang Xianbin Ma Yao Xiao Tian Zhang Leilei Yang Shaochen Yang Mengyun Liang Shuo Wang Zhizhong Wu Zhigang Xu Zhijun Sun | 2022 | Acta Pharmaceutica Sinica B2022，12，7： | 0 |
| 3 | 基于肿瘤微环境设计的高分子前药的研究进展显示文摘将药物改造成前药是修饰药物的一种常用手段,现已被广泛应用于抗肿瘤药物的设计中,其不仅可以改变母药溶解性,提高生物利用度,还能实现母药的靶向性。高分子前药作为前药设计的一个重要分支,既能发挥前药的优势,又能避免小分子药物在体内易被清除、选择性差等问题。笔者根据高分子前药的分类和设计原理,对近年来应用于抗肿瘤领域的靶向抗肿瘤高分子前药的研究情况和应用进行了综述。 | 徐玉怡 王东凯 | 2023 | 中国药剂学杂志(网络版)2023，21，3： | 0 |
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