We present here the results of a first-in-human, first-in-child trial for patients with relapsed/refractory solid tumors using Celyvir, an advanced therapy medicine that combines autologous mesenchymal stem cells (MSCs) carrying an oncolytic adenovirus. Celyvir was manufactured from a bone marrow aspirate and then given intravenously. Patients received weekly infusions for 6 weeks at a dose of 2 × 106 cells/kg (children) or 0.5-1 × 106 cells/kg (adults), 2 × 104 viral particles per cell. Fifteen pediatric and 19 adult patients were recruited, but 18 were screen failures, mainly because rapid disease progression before Celyvir was available. No grade 2-5 toxicities were reported. Adenoviral replication detected by PCR was found in all but 2 pediatric patient and in none of the adult ones. Absolute numbers of circulating leukocytes suffered minor changes along therapy, but some subsets showed differences comparing the pediatric versus the adult cohorts. Two patients with neuroblastoma showed disease stabilization, and one of them continued on treatment for up to 6 additional weeks. Celyvir, the combination of MSCs and oncolytic adenovirus, is safe and warrants further evaluation in a phase 2 setting. The use of MSCs may be a strategy to increase the amount of oncolytic virus administered to patients, minimizing toxicities and avoiding direct tumor injections.

中文翻译：

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晚期肿瘤患者中携带溶瘤病毒Icovir-5的自体MSC的首次人类首次试验。

我们在此介绍使用Celyvir（一种结合了携带溶瘤腺病毒的自体间充质干细胞（MSC）的先进治疗药物）用于复发/难治性实体瘤患者的首次人类，首次儿童试验的结果。Celyvir由骨髓穿刺液制成，然后静脉注射。患者每周接受2个106个细胞/ kg（儿童）或0.5-1个106个细胞/ kg（成人）的剂量，为期6周，每个细胞2个104个病毒颗粒。招募了15名儿科患者和19名成年患者，但18例筛查失败，主要是因为在使用Celyvir之前疾病迅速进展。没有报道2-5级毒性。通过PCR检测到的腺病毒复制在除2名儿童患者之外的所有患者中均未发现，而在成年患者中均未发现。在治疗过程中，循环白细胞的绝对数量发生微小变化，但有些子集显示儿科和成人队列之间存在差异。两名神经母细胞瘤患者表现出疾病稳定，其中一名继续接受长达6周的治疗。Celyvir是MSC和溶瘤腺病毒的组合，是安全的，需要在第二阶段进行进一步评估。MSC的使用可能是增加向患者施用溶瘤病毒的量，最大程度降低毒性并避免直接注射肿瘤的一种策略。MSC和溶瘤腺病毒的组合是安全的，并且需要在第二阶段进行进一步评估。MSC的使用可能是增加向患者施用溶瘤病毒的量，最大程度降低毒性并避免直接注射肿瘤的一种策略。MSC和溶瘤腺病毒的组合是安全的，并且需要在第二阶段进行进一步评估。MSC的使用可能是增加向患者施用溶瘤病毒的量，最大程度降低毒性并避免直接注射肿瘤的一种策略。