Molecular therapy oncolytics | VOL. 25
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Efficacy of a third-generation oncolytic herpes simplex virus in refractory soft tissue sarcoma xenograft models.

Publication Date Jun 16, 2022

Abstract

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. Invitro, six human cell lines and one mouse sarcoma cell line were assessed for T-01 cytotoxicity. Invivo, 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.

Concepts
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Refractory Sarcoma
Mouse Sarcoma Cell Line
Peritoneal Dissemination Model
Mouse Sarcoma Cell
Mouse Sarcoma
Xenotransplantation Model
Herpes Simplex Virus
ELISpot Assay
Sarcoma Cell
Cell Lines

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