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Abstract：
Sarcoma is derived from mesenchymal neoplasms and has numerous subtypes, accounting for 1% of all adult malignancies and 15% of childhood malignancies. The prognosis of metastatic or recurrent sarcoma remains poor. The current study presents two cases of sarcoma enrolled in a phase I dose escalation trial for solid tumor, who had previously failed all standard therapies. These patients were treated with VG161, an immune-stimulating herpes simplex virus type 1 oncolytic virus with payloads of IL-12, IL-15 and IL-15 receptor α unit, and a programmed cell death 1 (PD-1)/PD-1 ligand 1 blocking peptide. Both cases demonstrated stable disease as the best response, accompanied by a noteworthy prolongation of progression-free survival (11.8 months for chondrosarcoma and 11.9 months for soft tissue sarcoma, respectively) at a dose of 2.5×108 PFU/cycle. In addition, the treatment led to the activation of anti-cancer immunity, as evident from cytokine, lymphocyte subset and related pathway analyses of peripheral blood and/or tumor biopsy samples. These promising results suggest that VG161 monotherapy holds promise as an effective treatment for sarcoma and warrants further investigation through clinical trials. The two reported patients were part of a phase I clinical trial conducted and registered on the Australian New Zealand Clinical Trials Registry in Australia (registration no. ACTRN12620000244909; registration date, 26 February, 2020).
摘要：
肉瘤来源于间充质肿瘤，有许多亚型，占所有成人恶性肿瘤的1%和儿童恶性肿瘤的15%。转移性或复发性肉瘤的预后仍然较差。目前的研究提出了两例肉瘤，他们参加了实体肿瘤的I期剂量递增试验，以前所有标准疗法都失败了。这些患者接受了VG161治疗，VG161是一种免疫刺激的单纯疱疹病毒1型溶瘤病毒，具有IL-12，IL-15和IL-15受体α单位的有效载荷，和程序性细胞死亡1(PD-1)/PD-1配体1阻断肽。两种情况都证明疾病稳定是最好的反应，伴随着无进展生存期的显著延长（软骨肉瘤11.8个月，软组织肉瘤11.9个月，分别），剂量为2.5×108PFU/周期。此外,这种治疗导致了抗癌免疫力的激活，从细胞因子中可以明显看出，外周血和/或肿瘤活检样本的淋巴细胞亚群和相关通路分析。这些有希望的结果表明，VG161单一疗法有望作为肉瘤的有效治疗方法，并需要通过临床试验进行进一步研究。报告的两名患者是进行的I期临床试验的一部分，并在澳大利亚的澳大利亚新西兰临床试验注册中心注册（注册编号：ACTRN12620000244909；注册日期，2月26日,2020）。
