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

Kiyohara, Eiji; Tanemura, Atsushi; Nishioka, Motomu; Yamada, Miki; Tanaka, Aya; Yokomi, Akinori; Saito, Atsuhiro; Sakura, Kazuma; Nakajima, Takeshi; Myoui, Akira; Sakurai, Toshiharu; Kawakami, Yutaka; Kaneda, Yasufumi; Katayama, Ichiro

doi:10.1007/s00262-020-02509-8

Cited by 12 publications

(13 citation statements)

References 32 publications

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“…Currently, several clinical trials using HVJ‐E (GEN0101, manufactured by GenomIdea, Inc., Osaka, Japan) against malignant melanoma and malignant mesothelioma are ongoing in Japan. HVJ‐E is well tolerated and safe for clinical use 39,40 . Moreover, HVJ‐E is more effective in human‐derived tumors than in mouse‐derived tumors because of the direct killing effects of HVJ‐E on malignant cells by apoptosis 41 and necroptosis 42 .…”

Section: Discussionmentioning

confidence: 99%

“…HVJ-E is well tolerated and safe for clinical use. 39,40 Moreover, HVJ-E is more effective in human-derived tumors than in mouse-derived tumors because of the direct killing effects of HVJ-E on malignant cells by apoptosis 41 and necroptosis. 42 Therefore, we expect the combination of HVJ-E and siRNA-mediated PD-L1 knockdown therapy to be more potent for clinical use in human patients.…”

Section: Discussionmentioning

confidence: 99%

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Hemagglutinating virus of Japan‐envelope containing programmed cell death‐ligand 1 siRNA inhibits immunosuppressive activities and elicits antitumor immune responses in glioma

et al. 2020

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hemagglutinating virus of Japan‐envelope containing programmed cell death‐ligand 1 siRNA inhibits immunosuppressive activities and elicits antitumor immune responses in glioma

et al. 2020

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“…The recent UMIN000012943 phase 1 clinical study confirmed the tolerability of HVJ-E treatment at higher doses (30,000 and 60,000 mNAU) [93]. This result led to phase 1/2 clinical trials that combines HVJ-E with pembrolizumab to demonstrate the ability of HVJ-E in augmenting the antitumour immunity of ICB [122].…”

Section: Clinical Trials Based On Oncolytic Virusesmentioning

confidence: 92%

“…Overall, these results suggested the bystander effect caused the HVJ-E administration. The antitumour effects on target lesions are reinforced in a dose-dependent manner considering that complete and partial responses were observed in 33% of low-dose group and in 58% of high-dose group [122].…”

Section: Clinical Trials Based On Oncolytic Virusesmentioning

confidence: 99%

The Innate Immune Signalling Pathways: Turning RIG-I Sensor Activation against Cancer

Iurescia

Fioretti

Rinaldi

2020

Cancers

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Over the last 15 years, the ability to harness a patient’s own immune system has led to significant progress in cancer therapy. For instance, immunotherapeutic strategies, including checkpoint inhibitors or adoptive cell therapy using chimeric antigen receptor T-cell (CAR-T), are specifically aimed at enhancing adaptive anti-tumour immunity. Several research groups demonstrated that adaptive anti-tumour immunity is highly sustained by innate immune responses. Host innate immunity provides the first line of defence and mediates recognition of danger signals through pattern recognition receptors (PRRs), such as cytosolic sensors of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular pattern (DAMP) signals. The retinoic acid-inducible gene I (RIG-I) is a cytosolic RNA helicase, which detects viral double-strand RNA and, once activated, triggers signalling pathways, converging on the production of type I interferons, proinflammatory cytokines, and programmed cell death. Approaches aimed at activating RIG-I within cancers are being explored as novel therapeutic treatments to generate an inflammatory tumour microenvironment and to facilitate cytotoxic T-cell cross-priming and infiltration. Here, we provide an overview of studies regarding the role of RIG-I signalling in the tumour microenvironment, and the most recent preclinical studies that employ RIG-I agonists. Lastly, we present a selection of clinical trials designed to prove the antitumour role of RIG I and that may result in improved therapeutic outcomes for cancer patients.

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“…Not only apoptosis but also necroptosis was caused by HJV-E in neuroblastoma [ 8 ]. Since HVJ-E exerts an antitumor effect via the above diverse mechanism, we performed a first-in-human phase I/IIa dose-escalation clinical study for patients with advanced melanoma that could be treated intratumorally by HVJ-E at 1000 and 3000 milli neuraminidase units (mNAU) [ 9 ]. As a result, the safety and tolerability were confirmed with no dose-limiting toxicity (DLT).…”

Section: Introductionmentioning

confidence: 99%

A phase I dose-escalation, safety/tolerability, and preliminary efficacy study of the intratumoral administration of GEN0101 in patients with advanced melanoma

Kiyohara

Tanemura

Sakura

et al. 2022

Cancer Immunol Immunother

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Despite recent advance in immunotherapy agents, safe new therapies that enhance the effects of immune checkpoint inhibitors are still required to develop. 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 (n = 3 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-γ 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.

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

Cited by 12 publications

References 32 publications

Hemagglutinating virus of Japan‐envelope containing programmed cell death‐ligand 1 siRNA inhibits immunosuppressive activities and elicits antitumor immune responses in glioma

Hemagglutinating virus of Japan‐envelope containing programmed cell death‐ligand 1 siRNA inhibits immunosuppressive activities and elicits antitumor immune responses in glioma

The Innate Immune Signalling Pathways: Turning RIG-I Sensor Activation against Cancer

A phase I dose-escalation, safety/tolerability, and preliminary efficacy study of the intratumoral administration of GEN0101 in patients with advanced melanoma

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