评估HSV G207单独或单次放射剂量治疗进展性或复发性恶性脑幕上肿瘤儿童的I期临床试验的基本原理和设计

Q1 Medicine
A. M. Waters, J. Johnston, A. Reddy, J. Fiveash, A. Madan-Swain, K. Kachurak, A. Bag, G. Gillespie, J. Markert, G. Friedman
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引用次数: 5

摘要

原发性中枢神经系统肿瘤是儿童最常见的实体肿瘤,也是儿童癌症相关死亡的主要原因。儿童恶性幕上脑肿瘤的存活率很低,尽管积极的治疗联合手术,放疗和化疗;目前的治疗方法往往会给幸存者带来终生的后遗症。迫切需要创新的治疗方法。一种有希望的新方法是使用一种基因工程的、有条件地复制的单纯疱疹病毒(HSV),这种病毒在治疗恶性脑肿瘤方面显示出肿瘤特异性和潜在的疗效。G207是一种基因工程的HSV-1,缺乏在正常脑细胞中复制所必需的基因。在高度hsv敏感的猫头鹰猴(Aotus nancymai)颅内接种的临床前研究以及在复发/进行性高级别胶质瘤的三个成人I期试验中,安全性已得到证实。在成人研究中未发现剂量限制性毒性,也未达到最大耐受剂量。在35名接受治疗的成年人中,大约有一半在至少一个时间点有放射学或神经病理学的反应证据。儿童脑肿瘤模型的临床前研究表明,多种儿童肿瘤类型对G207杀伤高度敏感。本临床方案概述了人类儿童肿瘤内溶瘤病毒接种的首次研究,通过导管直接放置在复发或进展的幕上恶性肿瘤中。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Rationale and Design of a Phase I Clinical Trial to Evaluate HSV G207 Alone or with a Single Radiation Dose in Children with Progressive or Recurrent Malignant Supratentorial Brain Tumors.
Primary central nervous system tumors are the most common solid neoplasm of childhood and the leading cause of cancer related death in pediatric patients. Survival rates for children with malignant supratentorial brain tumors are poor despite aggressive treatment with combinations of surgery, radiation, and chemotherapy; and survivors often suffer from damaging lifelong sequelae from current therapies. Novel innovative treatments are greatly needed. One promising new approach is the use of a genetically engineered, conditionally replicating herpes simplex virus (HSV) that has shown tumor specific tropism and potential efficacy in the treatment of malignant brain tumors. G207 is a genetically engineered HSV-1 lacking genes essential for replication in normal brain cells. Safety has been established in preclinical investigations involving intracranial inoculation in the highly HSV-sensitive owl monkey (Aotus nancymai), and in three adult phase I trials in recurrent/progressive high-grade gliomas. No dose-limiting toxicities were seen in the adult studies and a maximum tolerated dose was not reached. Approximately half of the 35 treated adults had radiographic or neuropathologic evidence of response at a minimum of one time point. Preclinical studies in pediatric brain tumor models indicate that a variety of pediatric tumor types are highly sensitive to killing by G207. This clinical protocol outlines a first in human children study of intratumoral inoculation of an oncolytic virus via catheters placed directly into recurrent or progressive supratentorial malignant tumors.
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来源期刊
Human Gene Therapy Clinical Development
Human Gene Therapy Clinical Development CRITICAL CARE MEDICINEMEDICINE, RESEARCH &-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
7.20
自引率
0.00%
发文量
0
期刊介绍: Human Gene Therapy (HGT) is the premier, multidisciplinary journal covering all aspects of gene therapy. The Journal publishes important advances in DNA, RNA, cell and immune therapies, validating the latest advances in research and new technologies.
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