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

Sakura, Kazuma; Kuroyama, Muneyoshi; Shintani, Yasushi; Funaki, Soichiro; Atagi, Shinji; Kadota, Yoshihisa; Kuribayashi, Kozo; Kijima, Takashi; Nakano, Takashi; Nakajima, Toshihiro; Sasai, Masao; Okumura, Meinoshin; Kaneda, Yasufumi

doi:https://doi.org/10.1007/s00262-024-03815-1

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

Sakura, Kazuma; Kuroyama, Muneyoshi; Shintani, Yasushi et al.

Cancer Immunology, Immunotherapy, 2024, 73(12), 243

Number of Access:1,068（2025-08-14 18:26 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/98389

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Title	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
Creator	NRID 1000010432543 1000010432543 researchmap permalink 44sakuRa44 44sakuRa44 Scopus Author ID 57203892497 57203892497 CreatorName Sakura, Kazuma
	NRID 1000050770830 1000050770830 CreatorName Kuroyama, Muneyoshi
	NRID 1000090572983 1000090572983 researchmap permalink shintani6384 shintani6384 Scopus Author ID 7103142734 7103142734 CreatorName Shintani, Yasushi
	NRID 1000050464251 1000050464251 researchmap permalink so1 so1 Scopus Author ID 14123352700 14123352700 CreatorName Funaki, Soichiro
	CreatorName Atagi, Shinji
	NRID 1000050464243 1000050464243 CreatorName Kadota, Yoshihisa
	NRID 1000050351804 1000050351804 CreatorName Kuribayashi, Kozo
	NRID 1000090372614 1000090372614 CreatorName Kijima, Takashi
	CreatorName Nakano, Takashi
	CreatorName Nakajima, Toshihiro
	NRID 1000070598680 1000070598680 researchmap permalink osaka-pmda-mhlw osaka-pmda-mhlw Scopus Author ID 24723183400 24723183400 CreatorName Sasai, Masao
	NRID 1000040252647 1000040252647 CreatorName Okumura, Meinoshin
	NRID 1000010177537 1000010177537 researchmap permalink YK-MWK0108 YK-MWK0108 CreatorName Kaneda, Yasufumi
Subject	Clinical trial
	Hemagglutinating virus of Japan envelope (HVJ-E)
	Malignant pleural mesothelioma;
	Phase I
Description	The version of record of this article, first published in Cancer Immunology, Immunotherapy, is available online at Publisher’s website: https://doi.org/10.1007/s00262-024-03815-1.
Abstract	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).
Publisher	Springer Science and Business Media Deutschland GmbH
Source Title	Cancer Immunology, Immunotherapy
Volume (Issue)	73(12)
Page	243
Date of Issued	2024-10-03
Language	English
Handle URL	https://hdl.handle.net/11094/98389
PISSN	03407004
eISSN	14320851
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1007/s00262-024-03815-1
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Cancer Immunology, Immunotherapy. 2024, 73(12), p. 243
DC.title	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
DC.creator	Sakura, Kazuma
	Kuroyama, Muneyoshi
	Shintani, Yasushi
	Funaki, Soichiro
	Atagi, Shinji
	Kadota, Yoshihisa
	Kuribayashi, Kozo
	Kijima, Takashi
	Nakano, Takashi
	Nakajima, Toshihiro
	Sasai, Masao
	Okumura, Meinoshin
	Kaneda, Yasufumi
DC.publisher	Springer Science and Business Media Deutschland GmbH
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-10-03
DC.identifier	https://doi.org/10.1007/s00262-024-03815-1
DC.subject	Clinical trial
	Hemagglutinating virus of Japan envelope (HVJ-E)
	Malignant pleural mesothelioma;
	Phase I
DC.description	The version of record of this article, first published in Cancer Immunology, Immunotherapy, is available online at Publisher’s website: https://doi.org/10.1007/s00262-024-03815-1.
DCTERMS.abstract	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).
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	98389
citation_title	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
citation_author	Sakura, Kazuma
	Kuroyama, Muneyoshi
	Shintani, Yasushi
	Funaki, Soichiro
	Atagi, Shinji
	Kadota, Yoshihisa
	Kuribayashi, Kozo
	Kijima, Takashi
	Nakano, Takashi
	Nakajima, Toshihiro
	Sasai, Masao
	Okumura, Meinoshin
	Kaneda, Yasufumi
citation_publisher	Springer Science and Business Media Deutschland GmbH
citation_language	English
citation_date	2024-10-03
citation_journal_title	Cancer Immunology, Immunotherapy
citation_volume	73
citation_issue	12
citation_firstpage	243
citation_doi	https://doi.org/10.1007/s00262-024-03815-1
citation_public_url	https://hdl.handle.net/11094/98389

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

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