Abstract
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.
Highlights
Advanced melanoma is refractory to anticancer drugs, and many new immunotherapies have been developed in response to this in recent years
We focused on the clinical usefulness of intratumoral oncolytic virotherapy instead of systemic therapy
Induced tumor-specific cytotoxic T lymphocytes (CTLs) were maintained even when dacarbazine was used in combination with Hemagglutinating virus of Japan (HVJ)-E for melanoma [6]
Summary
Advanced melanoma is refractory to anticancer drugs, and many new immunotherapies have been developed in response to this in recent years. While programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) inhibitors are superior to chemotherapy in terms of their clinical effectiveness for advanced melanoma patients, combination therapy with anti-PD-1 and antiCTLA4 antibodies can cause severe immune-related adverse events, which are sometimes life-threatening [1]. The appearance of vitiligo reflecting the results of the immune response was observed This result indicated that HVJ-E can activate tumor immunity and may be effective in combination with immune-checkpoints inhibitors. Subsequent to this favorable result, we planned to use higher doses of HVJ-E (GEN0101) at 30,000 and 60,000 mNAU in patients with stage IIIC-IV advanced melanoma
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
