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.

IF 4.6 2区 医学 Q2 IMMUNOLOGY Cancer Immunology, Immunotherapy Pub Date : 2024-10-03 DOI:10.1007/s00262-024-03815-1
Kazuma Sakura, Muneyoshi Kuroyama, Yasushi Shintani, Soichiro Funaki, Shinji Atagi, Yoshihisa Kadota, Kozo Kuribayashi, Takashi Kijima, Takashi Nakano, Toshihiro Nakajima, Masao Sasai, Meinoshin Okumura, Yasufumi Kaneda
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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).

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瘤内和皮下注射日本血凝病毒包膜(HVJ-E)对化疗耐药恶性胸膜间皮瘤的剂量递增、耐受性和疗效:一项临床试验。
日本血凝病毒包膜(HVJ-E)是一种灭活的仙台病毒颗粒,具有抗肿瘤作用,可诱导抗肿瘤免疫。然而,其剂量和疗效尚未得到验证。我们对化疗耐药的恶性胸膜间皮瘤(MPM)进行了 I 期临床研究,旨在通过剂量限制毒性确定 II 期研究的推荐剂量,并评估 HVJ-E 的初步疗效。HVJ-E 经瘤内和皮下给药给耐化疗 MPM 患者。虽然没有发生严重不良事件,但观察到了 HVJ-E 的已知不良事件。在采用改良的实体瘤反应评价标准(RECIST)进行的初步抗肿瘤疗效研究中,有三名低剂量患者的病情出现进展,而所有高剂量患者的病情均趋于稳定,疾病控制率(DCR)分别为0%和100%。此外,HVJ-E对RECIST标准修改后的DCR和靶病灶大小的基线变化(通过CT和SUL-peak;p
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来源期刊
CiteScore
10.50
自引率
1.70%
发文量
207
审稿时长
1 months
期刊介绍: Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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