CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Novel strategies exploiting interleukin-12 in cancer immunotherapy.
Novel strategies exploiting interleukin-12 in cancer immunotherapy.
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白细胞介素-12被认为是增强抗肿瘤免疫应答的有效制剂。它属于异二聚体细胞因子家族,在细胞免疫的上调和下调中发挥关键作用。自被发现以来,重组IL-12在啮齿动物肿瘤模型中被发现具有强效抗肿瘤作用,并迅速进入临床测试,但获益/毒性特征不理想。IL-12的局部递送显著改善了治疗指数,基于体内电穿孔编码IL-12的裸质粒DNA、mRNA制剂、病毒载体和肿瘤靶向融合蛋白的这一方法正在临床中应用。其他生物技术策略,如IL-12工程化的局部过继细胞疗法和前体细胞因子,也可用于改善结果并拓宽治疗窗口。此类基于局部IL-12的方法与检查点抑制剂的联合策略在临床前和早期临床试验中均产生了有前景的结果。
Interleukin-12 is considered a potent agent to enhance antitumor immune responses. It belongs to a family of heterodimeric cytokines with key roles in the up-regulation and down-regulation of cellular immunity. Since its discovery, recombinant IL-12 was found to exert potent antitumor effects in rodent tumor models and was rapidly tested in the clinic with an unfavorable benefit/toxicity profile.
Localized delivery of IL-12 dramatically improves the therapeutic index and this approach is being applied in the clinic based on in-vivo electroporation of naked plasmid DNA encoding IL-12, mRNA formulations, viral vectors and tumor-targeted fusion proteins.
Other biotechnology strategies such as IL-12-engineered local adoptive cell therapy and pro-cytokines can also be used to improve results and broaden the therapeutic window. Combination strategies of such localized IL-12-based approaches with checkpoint inhibitors are yielding promising results both preclinically and in the early-phase clinical trials.
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