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病毒载体治疗脑癌

发布时间:2012/4/29 8:06:51    发布者:中国中西医结合医学会    点击量:831

在治疗复发性脑癌病人的实践中,加州大学圣地亚哥摩尔癌症中心的研究人员和外科医生是第一个吃螃蟹人,他们将一种在研的病毒载体直接注入肿瘤中。这种治疗方法由Tocagen股份有限公司开发

 

这个临床试验针对恶性胶质瘤,此肿瘤是最致命脑肿瘤形式中的一种,象这种在研治疗法的临床试验可能会形成一种新的治疗选择。

对于一个新诊断的晚期神经胶质瘤病人,提供给他的当前标准护理包括手术切除尽可能多的肿瘤,及接下来的放疗与化疗。尽管有这些措施,但肿瘤通常还是会复发,这使此临床试验提上了议事日程。

这个临床试验主要研究Toca51(vocimagene amiretrorepvec)注射剂与缓释片Toca FC (氟胞嘧啶)的联合使用。Toca 511是一种逆转录病毒复制载体(RRV),可将胞嘧啶脱氨酶(CD)的基因选择性地递送入癌细胞。在Toca511遍布肿瘤后,可表达CD基因的癌细胞就能将氟胞嘧啶转化成抗癌药物5-氟尿嘧啶(5-FU)。在这项研究中,病人每个月循环口服Toca FC,持续6个月时间。

这可能提供一种摧毁癌细胞的方法,而且这种方法不破坏精细的神经循环。外科科学家Clark Chen博士观察了参与这项临床试验的首个服用Toca 511的病人。他结合断层扫描术和核磁共振成像(MRI)技术来监控病人,并通过神经导航软件计算来精确定位肿瘤中注射Toca 511的位置。病人在接受注射后第二天便可出院。

Tocagen公司在研的Toca 511 & Toca FC疗法是一个许多尖端技术联合应用的典型例子,这些技术在过去的三年内已产生。它是一种许多不同领域的公立与私立机构多年努力的结晶,其中包括分子生物学家、基础科学家、病毒学家、物理学家、数学家、计算机科学家、医生、制造专家、管理专家和肿瘤学家。

Kesari的博士论文主题是脑肿瘤的病毒治疗,他的研究激情一直持续了20年之久。在20年前,他开始这方面的研究,并亲身经历了象Toca 511这样的新技术从实验室到病床这个过程的完成。

这项临床试验是治疗能力上的一个提高,它源自尖端科学与创新思维的结合,能给病人提供更好的治疗效果。在圣地亚哥加州大学,这种治疗法正在被转化到脑疾病患者的治疗中 。

这项临床试验的参与者必须是18岁或年纪大一些,患单一复发性三级或四级胶质瘤,并曾进行过手术和化放疗。(生物谷bioon.com)

Treating Brain Cancer With Viral Vector

sciencedaily/Mar. 1, 2012

UC San Diego Moores Cancer Center researchers and surgeons are among the first in the nation to treat patients with recurrent brain cancer by directly injecting an investigational viral vector into their tumor. The treatment is being developed by a local San Diego Company, Tocagen Inc.

"This clinical trial targets glioblastoma -- one of the deadliest forms of brain tumor," said principal investigator Santosh Kesari, MD, PhD, director of neuro-oncology in the Moores Cancer Center and in the Department of Neurosciences at the University of California, San Diego. "Clinical trials of investigational therapies such as this may lead to new treatment options for patients battling this deadly disease."

The current standard of care for a newly diagnosed, high-grade glioma includes surgically removing as much of the tumor as possible, followed by radiation therapy and chemotherapy. Despite these measures, the tumor usually recurs making this trial a high priority.

The trial is investigating the use of Toca 511 (vocimagene amiretrorepvec), for injection in combination with Toca FC (flucytosine), extended-release tablets. Toca 511 is a retroviral replicating vector (RRV) that is designed to deliver a cytosine deaminase (CD) gene selectively to cancer cells. After allowing time for the administered Toca 511 to spread through the cancerous tumor those cancer cells expressing the CD gene can convert flucytosine into the anti-cancer drug 5-fluorouracil (5-FU). In this study, patients receive cycles of oral Toca FC monthly for up to six months.

"This may provide a way to destroy the cancer cells without disrupting delicate neurocircuitry," explained surgeon scientist Clark Chen, MD, PhD, director of stereotactic and radiosurgery, UC San Diego Moores Cancer Center and an investigator on the study. Chen administered Toca 511 into the first patients who have participated in this clinical trial at UC San Diego. "We fused the patient's CT scan to their MRI and used neuro-navigation software to calculate exactly where in the tumor we needed to place the injection of Toca 511. The patients were given the injection and discharged from the hospital the day after the procedure."

Co-investigator Bob Carter, MD, PhD, chief of the Division of Neurosurgery at UC San Diego Medical Center and Moores Cancer Center, noted that this novel agent is the culmination of years of multi-disciplinary efforts. "Tocagen's investigational therapy, Toca 511 & Toca FC, is a representative example of the culmination of many technological advances that have come to pass during the last three decades," said Carter. "It is a convergence of years of hard work by dedicated public and private practitioners in many different fields -- including molecular biologists, basic scientists, virologists, physicists, mathematicians, surgeons, computer scientists, manufacturing experts, regulatory experts, and oncologists."

For Kesari, whose doctoral thesis focused on viral therapy for brain tumors, this has been a passion for 20 years. "I started this kind of research two decades ago, and to see a new technology like Toca 511 advance from bench to bedside completes the circle. This is the moment physician-researchers live for."

"This trial is an exciting realization of the ability to help our patients that comes from outstanding science combined with innovative thinking and the desire to deliver compassionate care," said William C. Mobley, MD, PhD, chair of the Department of Neurosciences at the UC San Diego School of Medicine. "At UC San Diego, we are intent upon transforming the care of patients with disorders of the brain."

Participants in this clinical trial must be 18 years or older; have a single, recurrent Grade three or four glioma and have had prior surgery and chemoradiation.