<br>瘤内注射日本信封载体血凝病毒对晚期黑色素瘤产生抗肿瘤作用：一项 I/IIa 期临床研究。,Cancer Immunology, Immunotherapy

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瘤内注射日本信封载体血凝病毒对晚期黑色素瘤产生抗肿瘤作用：一项 I/IIa 期临床研究。
Cancer Immunology, Immunotherapy ( IF 4.6 ) Pub Date : 2020-02-11 , DOI: 10.1007/s00262-020-02509-8
Eiji Kiyohara ₁ , Atsushi Tanemura ₁ , Megumi Nishioka ₁ , Mizuho Yamada ₁ , Aya Tanaka ₁ , Akinori Yokomi ₁ , Atsuhiro Saito ₂ , Kazuma Sakura ₂ , Toshihiro Nakajima ₃ , Akira Myoui ₂ , Toshiharu Sakurai ₄ , Yutaka Kawakami ₄ , Yasufumi Kaneda ₅ , Ichiro Katayama ₁

Affiliation

日本血凝病毒（HVJ；仙台病毒）是一种具有细胞融合活性的RNA病毒。 HVJ-包膜 (HVJ-E) 是一种经过紫外线照射的 HVJ 颗粒，它会失去病毒复制和蛋白质合成活性，但保留细胞融合活性。我们最近报道 HVJ-E 对多种类型的肿瘤具有抗肿瘤作用。在这里，我们描述了一项针对接受 HVJ-E 瘤内给药的晚期黑色素瘤患者的首次人体 I/IIa 期研究的结果。主要目的是评估HVJ-E的安全性和耐受性，次要目的是检查客观肿瘤反应和抗肿瘤免疫。六名患有皮肤或淋巴转移的 IIIC 或 IV 期进行性恶性黑色素瘤患者入组。患者被分为两组（每组 n = 3）并接受低剂量和高剂量的 HVJ-E。 6名患者中的5名完成了4周的随访评估；一名患者因病情进展而停止治疗。在6个注射靶病灶中的3个（50%）、15个未注射靶病灶中的7个（47%）和21个靶病灶中的10个（48%）中观察到完全或部分反应。观察到抗肿瘤免疫的诱导：自然杀伤细胞的激活、外周血中干扰素-γ水平显着增加以及细胞毒性T细胞浸润到注射和未注射的肿瘤病灶中。因此，晚期黑色素瘤患者瘤内注射 HVJ-E 显示出安全性和耐受性，并且抗肿瘤免疫介导的肿瘤局部消退。结果表明，HVJ-E 可能是晚期黑色素瘤患者的一种新治疗方法。

"点击查看英文标题和摘要"

Intratumoral injection of hemagglutinating virus of Japan-envelope vector yielded an antitumor effect for advanced melanoma: a phase I/IIa clinical study.

Hemagglutinating virus of Japan (HVJ; Sendai virus) is an RNA virus that has cell fusion activity. HVJ-envelope (HVJ-E) is a UV-irradiated HVJ particle that loses viral replication and protein synthesis activity but retains cell fusion activity. We recently reported that HVJ-E has antitumor effects on several types of tumors. Here, we describe the results of a first-in-human phase I/IIa study in patients with advanced melanoma, receiving intratumoral administration of HVJ-E. The primary aim was to evaluate the safety and tolerability of HVJ-E, and the secondary aim was to examine the objective tumor response and antitumor immunity. Six patients with stage IIIC or IV progressive malignant melanoma with skin or lymph metastasis were enrolled. Patients were separated into two groups (n = 3 each) and received low and high doses of HVJ-E. Five of the six patients completed 4 weeks of follow-up evaluation; one patient discontinued treatment owing to progressive disease. Complete or partial responses were observed in 3 of 6 (50%) injected target lesions, 7 of 15 (47%) noninjected target lesions, and 10 of 21 (48%) target lesions. Induction of antitumor immunity was observed: activation of natural killer cells, a marked increase in interferon-γ levels in the peripheral blood, and infiltration of cytotoxic T cells into both injected and noninjected tumor lesions. Thus, intratumoral injection of HVJ-E in advanced melanoma patients showed safety and tolerability with local regression of the tumor mediated by antitumor immunity. The results suggest that HVJ-E might be a new treatment approach in patients with advanced melanoma.

更新日期：2020-02-11

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