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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 (<jats:italic>n<\/jats:italic>\u2009=\u20093 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-\u03b3 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.<\/jats:p>","DOI":"10.1007\/s00262-021-03122-z","type":"journal-article","created":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T00:10:46Z","timestamp":1641341446000},"page":"2041-2049","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A phase I dose-escalation, safety\/tolerability, and preliminary efficacy study of the intratumoral administration of GEN0101 in patients with advanced melanoma"],"prefix":"10.1007","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0436-4296","authenticated-orcid":false,"given":"Eiji","family":"Kiyohara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5239-8474","authenticated-orcid":false,"given":"Atsushi","family":"Tanemura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuma","family":"Sakura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Nakajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Myoui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Yamazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Kiyohara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Katayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Fujimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasufumi","family":"Kaneda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,5]]},"reference":[{"key":"3122_CR1","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/s40487-019-0096-8","volume":"7","author":"LB Kennedy","year":"2019","unstructured":"Kennedy LB, Salama AKS (2019) A review of immune-mediated adverse events in melanoma. 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Toshihiro Nakajima and Yasufumi Kaneda are stockholders (0.08% and 0.5%) in GenomIdea, Inc. The other authors declare no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was performed with the approval of the ethics committee at Osaka University Hospital (No. 135903 on Dec 17, 2013). The project was allocated at the Medical Center for Translational Research, No. GEN101-JM001. All procedures involving human participants were carried out in accordance with the ethical standards of the Osaka University Hospital, national research committee (the University Hospital Medical Information Network-UMIN000012943), and in line with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Written informed consent for protocol therapy, the analysis of patient samples, and the use of data for research and publication were obtained from all individual participants prior to treatment in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}