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Erschienen in: Cancer Immunology, Immunotherapy 6/2020

11.02.2020 | Clinical Trial Report

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

verfasst von: Eiji Kiyohara, Atsushi Tanemura, Megumi Nishioka, Mizuho Yamada, Aya Tanaka, Akinori Yokomi, Atsuhiro Saito, Kazuma Sakura, Toshihiro Nakajima, Akira Myoui, Toshiharu Sakurai, Yutaka Kawakami, Yasufumi Kaneda, Ichiro Katayama

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 6/2020

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Abstract

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.
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Metadaten
Titel
Intratumoral injection of hemagglutinating virus of Japan-envelope vector yielded an antitumor effect for advanced melanoma: a phase I/IIa clinical study
verfasst von
Eiji Kiyohara
Atsushi Tanemura
Megumi Nishioka
Mizuho Yamada
Aya Tanaka
Akinori Yokomi
Atsuhiro Saito
Kazuma Sakura
Toshihiro Nakajima
Akira Myoui
Toshiharu Sakurai
Yutaka Kawakami
Yasufumi Kaneda
Ichiro Katayama
Publikationsdatum
11.02.2020
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 6/2020
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-020-02509-8

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