Dose-escalation, tolerability, and efficacy of intratumoral and subcutaneous injection of hemagglutinating virus of Japan envelope (HVJ-E) against chemotherapy-resistant malignant pleural mesothelioma: a clinical trial.

Autor: Sakura K; Respiratory Center, Osaka University Hospital, Suita, 5650871, Japan. sakura.kazuma.med@osaka-u.ac.jp.; Department of Surgery, Osaka University Graduate School of Medicine, Suita, 5650871, Japan. sakura.kazuma.med@osaka-u.ac.jp., Kuroyama M; Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, 5650871, Japan., Shintani Y; Respiratory Center, Osaka University Hospital, Suita, 5650871, Japan.; Department of Surgery, Osaka University Graduate School of Medicine, Suita, 5650871, Japan., Funaki S; Respiratory Center, Osaka University Hospital, Suita, 5650871, Japan.; Department of Surgery, Osaka University Graduate School of Medicine, Suita, 5650871, Japan.; Department of thoracic surgery, Hyogo Medical University, Nishinomiya, 6638501, Japan., Atagi S; Department of Thoracic Oncology, National Hospital Organization, Kinki-Chuo Chest Medical Center, Sakai, 5918555, Japan., Kadota Y; Department of Thoracic Surgery, Osaka Habikino Medical Center, Habikino, 5838588, Japan., Kuribayashi K; Division of Respiratory Medicine, Department of Internal Medicine, Hyogo Medicine University, Nishinomiya, 6638501, Japan., Kijima T; Division of Respiratory Medicine, Department of Internal Medicine, Hyogo Medicine University, Nishinomiya, 6638501, Japan., Nakano T; Division of Respiratory Medicine, Otemae Hospital, Osaka, 5400008, Japan., Nakajima T; Immunomedicine Inc., Osaka, 5410051, Japan., Sasai M; Department of Medical Innovation, Osaka University Hospital, Suita, 5650871, Japan., Okumura M; Department of Respiratory Surgery, National Hospital Organization, National Toneyama Hospital, Toyonaka, 5608552, Japan., Kaneda Y; Administration Bureau, Osaka University, Suita, 5650871, Japan.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2024 Oct 03; Vol. 73 (12), pp. 243. Date of Electronic Publication: 2024 Oct 03.
DOI: 10.1007/s00262-024-03815-1
Abstrakt: The hemagglutinating virus of Japan envelope (HVJ-E) is an inactivated Sendai virus particle with antitumor effect and inducing antitumor immunity. However, its dosage and efficacy have not been verified. We conducted a phase I clinical study on chemotherapy-resistant malignant pleural mesothelioma (MPM) aiming to determine the recommended dosage for a phase II study through dose-limiting toxicity and evaluate HVJ-E's preliminary efficacy. HVJ-E was administered intratumorally and subcutaneously to the patients with chemotherapy-resistant MPM. While no serious adverse events occurred, known adverse events of HVJ-E were observed. In the preliminary antitumor efficacy using modified response evaluation criteria in solid tumors (RECIST) criteria, three low-dose patients exhibited progressive disease, while all high-dose patients achieved stable disease, yielding disease control rates (DCRs) of 0% and 100%, respectively. Furthermore, the dose-dependent effect of HVJ-E revealed on DCR modified by RECIST and the baseline changes in target lesion size (by CT and SUL-peak; p < 0.05). Comparing targeted lesions receiving intratumoral HVJ-E with non-injected ones, while no clear difference existed at the end of the study, follow-up cases suggested stronger antitumor effects with intratumoral administration. Our findings suggest that HVJ-E could be safely administered to patients with chemotherapy-resistant MPM at both study doses. HVJ-E exhibited some antitumor activity against chemotherapy-resistant MPM, and higher doses tended to have stronger antitumor effects than lower doses. Consequently, a phase II clinical trial with higher HVJ-E doses has been conducted for MPM treatment. Trial registration number: UMIN Clinical Trials Registry (#UMIN000019345).
(© 2024. The Author(s).)
Databáze: MEDLINE
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