Dey Mahua, Auffinger Brenda, Lesniak Maciej S, Ahmed Atique U
The Brain Tumor Center, The University of Chicago Pritzker School of Medicine, 5841 South Maryland Avenue, MC 3026, Chicago, IL 60637, USA.
Future Virol. 2013 Jul;8(7):675-693. doi: 10.2217/fvl.13.47.
Initial observations from as early as the mid-1800s suggested that patients suffering from hematological malignancies would transiently go into remission upon naturally contracting viral infections laid the foundation for the oncolytic virotherapy research field. Since then, research focusing on anticancer oncolytic virotherapy has rapidly evolved. Today, oncolytic viral vectors have been engineered to stimulate and manipulate the host immune system, selectively targeting tumor tissues while sparing non-neoplastic cells. Glioblastoma multiforme, the most common adult primary brain tumor, has a disasterous history. It is one of the most deadly cancers known to humankind. Over the last century our understanding of this disease has grown exponentially. However, the median survival of patients suffering from this disease has only been extended by a few months. Even with the best, most aggressive modern therapeutic approaches available, malignant gliomas are still virtually 100% fatal. Motivated by the desperate need to find effective treatment strategies, more investments have been applied to oncolytic virotherapy preclinical and clinical studies. In this review we will discuss the antiglioma oncolytic virotherapy research field. We will survey its history and the principles laid down to serve as basis for preclinical works. We will also debate the variety of viral vectors used, their clinical applications, the lessons learned from clinical trials and possible future directions.
早在19世纪中叶的初步观察表明，血液系统恶性肿瘤患者在自然感染病毒后会短暂缓解，这为溶瘤病毒疗法研究领域奠定了基础。从那时起，专注于抗癌溶瘤病毒疗法的研究迅速发展。如今，溶瘤病毒载体经过改造，可刺激和操纵宿主免疫系统，选择性地靶向肿瘤组织，同时避免损伤非肿瘤细胞。多形性胶质母细胞瘤是最常见的成人原发性脑肿瘤，其治疗史十分惨痛。它是人类已知的最致命癌症之一。在过去的一个世纪里，我们对这种疾病的认识呈指数级增长。然而，患有这种疾病的患者的中位生存期仅延长了几个月。即使采用现有的最佳、最积极的现代治疗方法，恶性胶质瘤实际上仍然是100%致命的。出于寻找有效治疗策略的迫切需要，更多的投资已应用于溶瘤病毒疗法的临床前和临床研究。在这篇综述中，我们将讨论抗胶质瘤溶瘤病毒疗法研究领域。我们将审视其历史以及作为临床前研究基础的原则。我们还将讨论所使用的各种病毒载体、它们的临床应用、从临床试验中吸取的教训以及可能的未来方向。
