Department of Pediatric Research, University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Front Immunol. 2022 Sep 20;13:952231. doi: 10.3389/fimmu.2022.952231. eCollection 2022.
Interleukin 12 (IL-12) is a naturally occurring cytokine that plays a key role in inducing antitumor immune responses, including induction of antitumor immune memory. Currently, no IL-12-based therapeutic products have been approved for clinical application because of its toxicities. On the basis of this review of clinical trials using primarily wild-type IL-12 and different delivery methods, we conclude that the safe utilization of IL-12 is highly dependent on the tumor-specific localization of IL-12 post administration. In this regard, we have developed a cell membrane-anchored and tumor-targeted IL-12-T (attIL12-T) cell product for avoiding toxicity from both IL-12 and T cells-induced cytokine release syndrome in peripheral tissues. A phase I trial using this product which seeks to avoid systemic toxicity and boost antitumor efficacy is on the horizon. Of note, this product also boosts the impact of CAR-T or TCR-T cell efficacy against solid tumors, providing an alternative approach to utilize CAR-T to overcome tumor resistance.
白细胞介素 12（IL-12）是一种天然存在的细胞因子，在诱导抗肿瘤免疫反应中发挥关键作用，包括诱导抗肿瘤免疫记忆。目前，由于其毒性，尚无基于白细胞介素 12 的治疗产品获得临床应用批准。基于对主要使用野生型白细胞介素 12 和不同递送方法的临床试验的回顾，我们得出结论，安全利用白细胞介素 12 高度依赖于给药后白细胞介素 12 在肿瘤部位的特异性定位。在这方面，我们开发了一种细胞膜锚定和肿瘤靶向的白细胞介素 12-T（attIL12-T）细胞产品，用于避免白细胞介素 12 和 T 细胞诱导的细胞因子释放综合征在周围组织中的毒性。一项使用该产品的 I 期临床试验旨在避免全身毒性并提高抗肿瘤疗效，即将进行。值得注意的是，该产品还提高了 CAR-T 或 TCR-T 细胞对实体瘤的疗效，为利用 CAR-T 克服肿瘤耐药性提供了一种替代方法。
