Melanoma treatment with intratumoral electroporation of tavokinogene telseplasmid (pIL-12, tavokinogene telseplasmid)
Melanoma treatment with intratumoral electroporation of tavokinogene telseplasmid (pIL-12, tavokinogene telseplasmid)
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DOI：
10.2217/imt-2017-0096
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发表时间：
2017-12-01
期刊：
影响因子：
2.8
通讯作者：
Algazi, Alain
中科院分区：
文献类型：
--
作者：
Canton, David A.;Shirley, Shawna;Algazi, Alain
肿瘤通过多种机制逃避免疫系统的检测和/或清除。IL-12是一种有效的免疫调节细胞因子，在免疫引发中起着重要作用。然而，IL-12的全身递送可导致危及生命的毒性，因此在可安全施用的剂量下显示出有限的功效。我们开发了一种电穿孔技术，在肿瘤内产生高度局部化的IL-12表达，导致动物模型和患者中治疗和未治疗病变的消退，具有良好的安全性。此外，肿瘤内tavokinogene telseplasmid电穿孔可以驱动细胞免疫应答，将“冷”肿瘤转化为“热”肿瘤。临床试验正在进行中，以确定肿瘤内tavokinogene telseplasmid电穿孔是否与预测对PD-1抗体单一疗法无反应的免疫学冷肿瘤中的检查点阻断疗法协同作用。
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.