Efficacy of a third-generation oncolytic herpes simplex virus in refractory soft tissue sarcoma xenograft models.
Efficacy of a third-generation oncolytic herpes simplex virus in refractory soft tissue sarcoma xenograft models.
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DOI：
10.1016/j.omto.2022.04.010
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发表时间：
2022-06-16
期刊：
影响因子：
--
通讯作者：
Sekimoto, Mitsugu
中科院分区：
文献类型：
--
作者：
Hatta, Masahiko;Kaibori, Masaki;Matsushima, Hideyuki;Yoshida, Terufumi;Okumura, Tadayoshi;Hayashi, Mikio;Yoshii, Kengo;Todo, Tomoki;Sekimoto, Mitsugu
恶性软组织肿瘤，特别是高度恶性的平滑肌肉瘤，对化疗有抵抗力，预后差。T-01是一种第三代遗传修饰的单纯疱疹病毒1型，仅在肿瘤细胞中复制，并发挥细胞杀伤作用。本研究旨在探讨T-01的抗肿瘤作用，这是一种治疗平滑肌肉瘤的新方法。在体外，评估了6种人细胞系和1种小鼠肉瘤细胞系的T-01细胞毒性。在体内，在皮下移植的平滑肌肉瘤（SK-LMS-1）细胞和皮下或腹腔内移植的小鼠肉瘤（CCRF S-180 II）细胞中检查了T-01的功效。使用来自同种异体模型的脾细胞的ELISpot测定评估细胞因子用于免疫学评价。T-01在所有七种细胞系中显示细胞毒性（p < 0.001）。在SK-LMS-1异种移植模型中，T-01给药抑制了肿瘤生长（p = 0.02）。在CCRF S-180 II皮下肿瘤模型中，与对照组相比，T-01给药组的双侧肿瘤生长受到显著抑制（p < 0.001）。在腹膜播散模型中，与对照组相比，T-01治疗引起显著的存活延长（p < 0.01）。总之，第三代转基因单纯疱疹病毒1型可能是一种有效的新疗法对难治性肉瘤。T-01是第三代单纯疱疹病毒1型转基因疫苗，在小鼠横纹肌肉瘤和平滑肌肉瘤模型中能有效抑制肿瘤生长。使用第三代oHSV的溶瘤病毒治疗可能是难治性肉瘤的一种新治疗方法。
Malignant soft tissue tumors, particularly highly malignant leiomyosarcomas, are resistant to chemotherapy and associated with a poor prognosis. T-01, a third-generation genetically modified herpes simplex virus type 1, replicates in tumor cells alone and exerts a cell-killing effect. The current study aimed to investigate the antitumor effect of T-01, which is a novel treatment for leiomyosarcoma. In vitro, six human cell lines and one mouse sarcoma cell line were assessed for T-01 cytotoxicity. In vivo, the efficacy of T-01 was examined in subcutaneously transplanted leiomyosarcoma (SK-LMS-1) cells and subcutaneously or intraperitoneally transplanted mouse sarcoma (CCRF S-180II) cells. Cytokines were assessed using ELISpot assay with splenocytes from the allogeneic models for immunological evaluation. T-01 showed cytotoxicity in all seven cell lines (p < 0.001). In the SK-LMS-1 xenotransplantation model, tumor growth was suppressed by T-01 administration (p = 0.02). In the CCRF S-180II subcutaneous tumor model, bilateral tumor growth was significantly suppressed in the T-01-treated group compared with the control group (p < 0.001). In the peritoneal dissemination model, T-01 treatment caused significant survival prolongation compared with the control (p < 0.01). In conclusion, third-generation genetically modified herpes simplex virus type 1 may be an effective novel therapy against refractory sarcomas. T-01, a third-generation genetically modified herpes simplex virus type 1, can effectively inhibit tumor growth in the mouse models of rhabdomyosarcoma and leiomyosarcoma. Oncolytic viral therapy using third-generation oHSV may be a novel treatment for refractory sarcoma.
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影响因子：
5.1
作者：
通讯作者：
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影响因子：
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作者：
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DOI：
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发表时间：
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期刊：
Molecular therapy oncolytics
影响因子：
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