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.

白细胞介素 12 被认为是增强抗肿瘤免疫反应的有效药物。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起关键作用。自发现以来，重组 IL-12 被发现在啮齿动物肿瘤模型中发挥有效的抗肿瘤作用，并在临床上快速测试，具有不利的益处/毒性特征。IL-12 的局部递送显着提高了治疗指数，并且这种方法正在基于体内应用于临床编码 IL-12 的裸质粒 DNA、mRNA 制剂、病毒载体和肿瘤靶向融合蛋白的电穿孔。其他生物技术策略，如 IL-12 改造的局部过继细胞疗法和前细胞因子，也可用于改善结果和拓宽治疗窗口。这种基于局部 IL-12 的方法与检查点抑制剂的组合策略在临床前和早期临床试验中都取得了有希望的结果。