Retroviral gene transfer of interleukin-12 (IL-12) into T cells markedly enhances antitumor efficacy upon adoptive transfer but has clinically shown unacceptable severe side effects. To overcome the toxicity, we engineered tumor-specific CD8+ T cells to transiently express IL-12. Engineered T cells injected intratumorally, but not intravenously, led to complete rejections not only of the injected lesion but also of distant concomitant tumors. Efficacy was further enhanced by co-injection with agonist anti-CD137 mAb or by transient co-expression of CD137 ligand. This treatment induced epitope spreading of the endogenous CD8+ T cell immune response in a manner dependent on cDC1 dendritic cells. Mouse and human tumor-infiltrating T lymphocyte cultures can be transiently IL-12 engineered to attain marked immunotherapeutic effects.

中文翻译：

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IL-12 mRNA瞬时改造的抗肿瘤CD8 + T细胞的肿瘤内过继转移。

将白细胞介素12（IL-12）逆转录病毒基因转移到T细胞中可显着增强过继转移后的抗肿瘤功效，但临床上已显示出不可接受的严重副作用。为了克服毒性，我们设计了肿瘤特异性CD8 + T细胞来瞬时表达IL-12。肿瘤内注射而非静脉内注射的工程化T细胞不仅导致注射病变的完全排斥，也导致远处伴随肿瘤的完全排斥。通过与激动剂抗CD137 mAb共同注射或通过CD137配体的瞬时共表达，进一步提高了疗效。这种治疗以依赖于cDC1树突状细胞的方式诱导了内源性CD8 + T细胞免疫反应的表位扩散。可以将小鼠和人类肿瘤浸润性T淋巴细胞培养物进行瞬时IL-12改造，以达到显着的免疫治疗效果。