不可逆电穿孔增强 CAR-T 细胞对实体瘤的浸润与选择性癌细胞裂解
Irreversible Electroporation Enhances Solid Tumor Infiltration and Selective Cancer Cell Lysis by CAR T Cells.
通过利用一种双用途转化策略——直接的癌细胞靶向细胞毒性和增强的 CAR-T 细胞浸润——sIRE 能够减轻肿瘤负荷,同时保持并增强 CAR-T 细胞功能。
肿瘤细胞治疗研究
英文原题:Add-On Effect of Hemagglutinating Virus of Japan Envelope Combined with Chemotherapy or Immune Checkpoint Inhibitor against Malignant Pleural Mesothelioma: An In Vivo Study.
Add-On Effect of Hemagglutinating Virus of Japan Envelope Combined with Chemotherapy or Immune Checkpoint Inhibitor against Malignant Pleural Mesothelioma: An In Vivo Study.
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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已经播散。此前,MPM的主要治疗方法是联合化疗。然而,近年来免疫检查点抑制剂(ICIs)也被用于治疗。为了提高MPM治疗的疗效,我们关注了日本血凝病毒包膜(HVJ-E),它可以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作为单药治疗或与化疗或ICIs联合治疗对荷MPM小鼠是否有效。
我们在荷MPM小鼠中确认了其抗肿瘤疗效。与对照小鼠相比,以及与CDDP联合使用时,HVJ-E显著延长了荷人MPM小鼠的生存期。这种疗效在NOD-SCID小鼠中消失,提示HVJ-E对先天免疫的激活与生存率相关。HVJ-E在荷鼠源MPM小鼠中也显示出抗肿瘤疗效。与单独化疗相比,化疗与HVJ-E联合导致细胞毒性T细胞(CTLs)显著增加,提示不仅HVJ-E激活的先天免疫,而且CTLs的增加也有助于改善生存。抗PD-1抗体与HVJ-E联合显著延长了荷鼠源MPM小鼠的生存率。
此外,HVJ-E可能通过维持针对肿瘤的免疫原性来发挥抗肿瘤作用。我们相信HVJ-E可能是一种有益的治疗方法,可在未来改善MPM的治疗。
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.
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