Sharma Anurag, Tandon Manish, Bangari Dinesh S, Mittal Suresh K
Department of Comparative Pathobiology, and Bindley Bioscience Center, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA.
Curr Drug ther. 2009 May 1;4(2):117-138. doi: 10.2174/157488509788185123.
Definitive treatment of cancer has eluded scientists for decades. Current therapeutic modalities like surgery, chemotherapy, radiotherapy and receptor-targeted antibodies have varied degree of success and generally have moderate to severe side effects. Gene therapy is one of the novel and promising approaches for therapeutic intervention of cancer. Viral vectors in general and adenoviral (Ad) vectors in particular are efficient natural gene delivery systems and are one of the obvious choices for cancer gene therapy. Clinical and preclinical findings with a wide variety of approaches like tumor suppressor and suicide gene therapy, oncolysis, immunotherapy, anti-angiogenesis and RNA interference using Ad vectors have been quite promising, but there are still many hurdles to overcome. Shortcomings like increased immunogenicity, prevalence of preexisting anti-Ad immunity in human population and lack of specific targeting limit the clinical usefulness of Ad vectors. In recent years, extensive research efforts have been made to overcome these limitations through a variety of approaches including the use of conditionally-replicating Ad and specific targeting of tumor cells. In this review, we discuss the potential strengths and limitations of Ad vectors for cancer therapy.
几十年来,科学家们一直未能找到癌症的根治方法。目前的治疗方式,如手术、化疗、放疗和受体靶向抗体,都有不同程度的成功,但通常伴有中度到重度的副作用。基因治疗是癌症治疗干预的一种新颖且有前景的方法。一般的病毒载体,特别是腺病毒(Ad)载体,是高效的天然基因递送系统,也是癌症基因治疗的明显选择之一。使用Ad载体进行肿瘤抑制和自杀基因治疗、溶瘤、免疫治疗、抗血管生成和RNA干扰等多种方法的临床和临床前研究结果很有前景,但仍有许多障碍需要克服。诸如免疫原性增加、人群中预先存在的抗Ad免疫以及缺乏特异性靶向等缺点限制了Ad载体的临床应用。近年来,人们通过多种方法,包括使用条件复制型Ad和肿瘤细胞的特异性靶向,进行了广泛的研究努力来克服这些限制。在这篇综述中,我们讨论了Ad载体用于癌症治疗的潜在优势和局限性。