静脉递送腺病毒载体在肿瘤基因治疗中的研究进展

Progress in systemic administration of adenovirus vector for cancer gene therapy

基因治疗已成为继手术切除、放疗、化疗和介入治疗之后又一种新的肿瘤治疗模式。肿瘤基因治疗能否成功的关键在于选择恰当载体。腺病毒被广泛用作基因治疗载体。基因工程改造后的溶瘤腺病毒具有肿瘤细胞特异性复制能力,在溶解被感染细胞的同时,还能高效表达所携带的目的基因,从而发挥抗肿瘤作用,因此其被认为是一种有效的肿瘤治疗策略。静脉递送对晚期转移肿瘤的治疗有重要作用,但以往的溶瘤腺病毒载体在体内递送局限于局部瘤内注射。由于溶瘤腺病毒在全身给药时存在肝内非特异性聚集和宿主免疫反应,而非病毒载体具有生物安全性好和免疫原性低等优点,因此两者联合应用将有助于溶瘤腺病毒的静脉递送。本文就近年来针对溶瘤腺病毒静脉递送用于肿瘤基因治疗的研究策略进行综述,重点阐述溶瘤腺病毒载体及非病毒载体联合应用于肿瘤基因治疗的研究进展。

Gene therapy has become a new cancer therapy model behind surgical excision, radiotherapy, chemotherapy and interventional therapy. The choice of proper carrier is very important in cancer gene therapy. Adenovirus is widely used as a vector carrier in cancer gene therapy. Gene-engineered oncolytic adenovirus （OncoAd） has the advantages including cancer cell-specific replication, infected cell destruction, and high expression of inserted therapeutic genes, so as to obtain the potent antitumor efficacy. Therefore, using OncoAd is considered to be an effective tumor therapy strategy. The systemic administration of intravenous delivery plays an important role in the treatment of advanced metastatic cancer. However, the delivery of OncoAd was limited to local injection in vivo in the past. Because the efficacy of intravenously administering OncoAd is compromised by non-specific sequestration in the liver and host immune response, while the non-viral vectors have the advantages of good biosafety and low immunogenicity, the combination of the two will be beneficial to the systemic administration of OncoAd. In this paper, the research strategies of OncoAd intravenous delivery for cancer gene therapy in recent years are reviewed, and the research progress in OncoAd combined with non-viral vector for cancer gene therapy is emphasized.