Department of Internal Medicine, College of Medicine, Pusan National University and Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Mol Ther. 2023 Jul 5;31(7):2077-2088. doi: 10.1016/j.ymthe.2023.04.006. Epub 2023 Apr 14.
OBP-301 is an oncolytic adenovirus modified to replicate within cancer cells and lyse them. This open-label, non-comparative, phase I dose-escalation trial aimed to assess its safety and optimal dosage in 20 patients with advanced hepatocellular carcinoma. Good tolerance was shown with a maximum tolerated dose of 6 × 10 viral particles. The most common treatment-emergent adverse events were influenza-like illness, pyrexia, fatigue, decreased platelet count, abdominal distension, and anemia. Cohorts 4 and 5 had approximately 50% higher levels of CD8+ T cells in the peripheral blood after injection. The best target response occurred in 14 patients, 4 of whom had progressive disease. Multiple intratumoral injections of OBP-301 were well tolerated in patients with advanced hepatocellular carcinoma. The stable disease rate for the injected tumors was greater than the overall response rate, even with no obvious tumor response. OBP-301 might have a greater impact on local response as histological examination revealed that the presence of OBP-301 was consistent with the necrotic area at the injection site. Increased infiltration of CD8+ T cells and <1% PD-L1 expression were observed in tumors after injection. Improved antitumor efficacy might be achieved in future studies via viral injection with volume adjustment and in combination with other immuno-therapeutics.
OBP-301 是一种经过改造的溶瘤腺病毒，可以在癌细胞内复制并裂解它们。这项开放标签、非对照、I 期剂量递增试验旨在评估其在 20 名晚期肝细胞癌患者中的安全性和最佳剂量。最大耐受剂量为 6×10 病毒颗粒时显示出良好的耐受性。最常见的治疗相关不良事件是流感样疾病、发热、疲劳、血小板计数减少、腹胀和贫血。注射后，第 4 组和第 5 组的外周血 CD8+T 细胞水平约升高 50%。14 名患者出现最佳目标反应，其中 4 名患者病情进展。在晚期肝细胞癌患者中，多次瘤内注射 OBP-301 耐受性良好。注射肿瘤的疾病稳定率大于总体反应率，即使没有明显的肿瘤反应。OBP-301 可能对局部反应有更大的影响，因为组织学检查显示 OBP-301 的存在与注射部位的坏死区域一致。注射后肿瘤中观察到 CD8+T 细胞浸润增加和<1%PD-L1 表达。通过调整病毒注射体积并与其他免疫疗法联合使用，未来的研究可能会提高抗肿瘤疗效。
