Sakura Kazuma, Sasai Masao, Funaki Soichiro, Shintani Yasushi, Okumura Meinoshin, Kaneda Yasufumi
Respiratory Center, Osaka University Hospital, 2-15, Yamadaoka, Suita 565-0871, Osaka, Japan.
Division of Translational Research, Osaka University Hospital, 2-15, Yamadaoka, Suita 565-0871, Osaka, Japan.
Cancers (Basel). 2023 Feb 1;15(3):929. doi: 10.3390/cancers15030929.
Malignant pleural mesothelioma (MPM) is a refractory tumor because most of the lesions are already disseminated at diagnosis. Previously, the main treatment for MPM was combination chemotherapy. However, recently, immune checkpoint inhibitors (ICIs) are also used. For better efficacy of MPM treatment, we focused on hemagglutinating virus of Japan envelope (HVJ-E), which activates antitumor immunity and induces tumor-specific cell death. In this paper, we aimed to determine whether HVJ-E as a single agent therapy or in combination with chemotherapy or ICIs is effective in MPM bearing mouse. We confirmed its antitumor efficacy in MPM-bearing mouse. HVJ-E significantly prolonged the survival of human MPM-bearing mouse compared to that of control mouse and when combined with CDDP. This efficacy was lost in NOD-SCID mouse, suggesting that activation of innate immunity by HVJ-E was related to the survival rate. HVJ-E also showed antitumor efficacy in murine MPM-bearing mouse. The combination of chemotherapy and HVJ-E caused a significant increase in cytotoxic T cells (CTLs) compared to chemotherapy alone, suggesting that not only innate immunity activated by HVJ-E but also the increase in CTLs contributed to improved survival. The combination of anti-PD-1 antibody and HVJ-E significantly prolonged the survival rate of murine MPM-bearing mouse. Further, HVJ-E might have exhibited antitumor effects by maintaining immunogenicity against tumors. We believe that HVJ-E may be a beneficial therapy to improve MPM treatment in the future.
恶性胸膜间皮瘤（MPM）是一种难治性肿瘤，因为大多数病变在诊断时就已经发生了扩散。以前，MPM的主要治疗方法是联合化疗。然而，最近也开始使用免疫检查点抑制剂（ICI）。为了提高MPM的治疗效果，我们聚焦于日本血凝病毒包膜（HVJ-E），它能激活抗肿瘤免疫并诱导肿瘤特异性细胞死亡。在本文中，我们旨在确定HVJ-E作为单一药物疗法或与化疗或ICI联合使用对携带MPM的小鼠是否有效。我们在携带MPM的小鼠中证实了其抗肿瘤效果。与对照小鼠相比，HVJ-E显著延长了携带人MPM小鼠的生存期，并且与顺铂联合使用时也是如此。在NOD-SCID小鼠中这种效果消失了，这表明HVJ-E对固有免疫的激活与生存率有关。HVJ-E在携带鼠源MPM的小鼠中也显示出抗肿瘤效果。与单独化疗相比，化疗与HVJ-E联合使用导致细胞毒性T细胞（CTL）显著增加，这表明不仅HVJ-E激活的固有免疫，而且CTL的增加都有助于提高生存率。抗PD-1抗体与HVJ-E联合使用显著延长了携带鼠源MPM小鼠的生存率。此外，HVJ-E可能通过维持对肿瘤的免疫原性而发挥抗肿瘤作用。我们相信HVJ-E未来可能是一种改善MPM治疗的有益疗法。
