Canton David A, Shirley Shawna, Wright Jocelyn, Connolly Richard, Burkart Christoph, Mukhopadhyay Anandaroop, Twitty Chris, Qattan Kristen E, Campbell Jean S, Le Mai H, Pierce Robert H, Gargosky Sharron, Daud Adil, Algazi Alain
OncoSec Medical Incorporated, 5820 Nancy Ridge Dr, San Diego, CA 92121, USA.
Fred Hutchinson Cancer Research Center, Clinical Research Division, 1100 Fairview Ave. N. Seattle, WA 98109, USA.
Immunotherapy. 2017 Dec;9(16):1309-1321. doi: 10.2217/imt-2017-0096. Epub 2017 Oct 24.
Tumors evade detection and/or clearance by the immune system via multiple mechanisms. IL-12 is a potent immunomodulatory cytokine that plays a central role in immune priming. However, systemic delivery of IL-12 can result in life-threatening toxicity and therefore has shown limited efficacy at doses that can be safely administered. We developed an electroporation technique to produce highly localized IL-12 expression within tumors leading to regression of both treated and untreated lesions in animal models and in patients with a favorable safety profile. Furthermore, intratumoral tavokinogene telseplasmid electroporation can drive cellular immune responses, converting 'cold' tumors into 'hot' tumors. Clinical trials are ongoing to determine whether intratumoral tavokinogene telseplasmid electroporation synergizes with checkpoint blockade therapy in immunologically cold tumors predicted not to respond to PD-1 antibody monotherapy.
肿瘤通过多种机制逃避免疫系统的检测和/或清除。白细胞介素-12（IL-12）是一种强效免疫调节细胞因子，在免疫启动中起核心作用。然而，全身性递送IL-12可导致危及生命的毒性，因此在可安全给药的剂量下疗效有限。我们开发了一种电穿孔技术，可在肿瘤内产生高度局部化的IL-12表达，导致动物模型和安全性良好的患者中治疗和未治疗的病变均出现消退。此外，肿瘤内注射他伏基因替列质粒电穿孔可驱动细胞免疫反应，将“冷”肿瘤转化为“热”肿瘤。目前正在进行临床试验，以确定肿瘤内注射他伏基因替列质粒电穿孔是否能与在预测对PD-1抗体单药治疗无反应的免疫冷肿瘤中的检查点阻断疗法协同作用。
