A phase I dose-escalation, safety/tolerability, and preliminary efficacy study of the intratumoral administration of GEN0101 in patients with advanced melanoma.
A phase I dose-escalation, safety/tolerability, and preliminary efficacy study of the intratumoral administration of GEN0101 in patients with advanced melanoma.
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DOI：
10.1007/s00262-021-03122-z
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发表时间：
2022-08
影响因子：
5.8
通讯作者：
Kaneda, Yasufumi
中科院分区：
文献类型：
--
作者：
Kiyohara, Eiji;Tanemura, Atsushi;Sakura, Kazuma;Nakajima, Toshihiro;Myoui, Akira;Yamazaki, Naoya;Kiyohara, Yoshio;Katayama, Ichiro;Fujimoto, Manabu;Kaneda, Yasufumi
关键词：
尽管最近在免疫治疗剂方面取得了进展，但仍需要开发增强免疫检查点抑制剂效果的安全新疗法。我们先前证明日本包膜血凝病毒（HVJ-E）不仅诱导直接肿瘤细胞死亡，而且通过激活T和自然杀伤（NK）细胞诱导抗肿瘤免疫，此后，开发了HVJ-E（GEN 0101）的生产工艺用于临床。我们在这里进行了一项肿瘤内给予GEN 0101的Ia期临床试验，治疗6例IIIC或IV期恶性黑色素瘤患者。主要目的是评估GEN 0101的安全性和耐受性，次要目的是检查客观肿瘤缓解。将患者分成两组（每组n = 3），并接受低剂量的30，000 mNAU和高剂量的60，000 mNAU的GEN 0101。所有患者均完成了为期两周的随访评估，无严重不良事件。总缓解率为33%（6例中的2例），高剂量组有2例部分缓解，低剂量组有2例疾病稳定，2例疾病进展。在18个靶病灶中的11个（61%）中观察到局部完全或部分缓解。1例患者治疗后肺转移灶缩小。NK细胞的活性和干扰素-γ水平在循环中增加，表明GEN 0101增强了抗肿瘤免疫力。该试验不仅显示了GEN 0101的安全性和耐受性，而且显示了显著的抗肿瘤作用，表明GEN 0101可能是治疗晚期黑色素瘤患者的有希望的新药。在线版本包含补充材料，可通过10.1007/s 00262 -021-03122-z获得。
Despite recent advance in immunotherapy agents, safe new therapies that enhance the effects of immune checkpoint inhibitors are still required to develop. We previously demonstrated that hemagglutinating virus of Japan-envelope (HVJ-E) induced not only direct tumor cell death but also antitumor immunity through the activation of T and natural killer (NK) cells, thereafter, developed a manufacturing process of HVJ-E (GEN0101) for clinical use. We here performed a phase Ia clinical trial of intratumoral GEN0101 administration in six patients with stage IIIC or IV malignant melanoma. The primary aim was to evaluate the safety and tolerability of GEN0101, and the secondary aim was to examine the objective tumor response. Patients were separated into two groups (n = 3 each) and received a low dose of 30,000 and high dose of 60,000 mNAU of GEN0101. All patients completed a two-week follow-up evaluation without severe adverse events. The overall response rate was 33% (2 of 6), with 2 partial responses in the high-dose group and 2 with stable disease, and 2 with progressive disease in the low-dose group. Local complete or partial responses were observed in 11 of 18 (61%) target lesions. One patient demonstrated shrinkage of lung metastases after the treatment. The activity of NK cells and interferon-γ levels were increased in the circulation, indicating augmentation of antitumor immunity by GEN0101. This trial showed not only the safety and tolerability but also the significant antitumor effect of GEN0101, suggesting that GEN0101 might be a promising new drug for patients with advanced melanoma. The online version contains supplementary material available at 10.1007/s00262-021-03122-z.
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影响因子：
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作者：
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通讯作者：
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