Antibody gene therapy: an attractive approach for the treatment of cancers and other chronic diseases

Monoclonal (mAb ) 成功地被用于长期的疾病的治疗，例如癌症，发炎和有免疫力的疾病。与在抗体工程的技术进展，当有减少的 immunogenicity 的高亲密关系治疗学在聚光灯下面变得，小重组体抗体的开发碎裂。设计重组体抗体碎片的一种流行格式是单个链的改正变量(scFv ) 分子，父母抗体的 VH 和 VL 区域被一个多肽连接器一起在连接。scFv 碎片保留目标特性和未经触动的抗体，和罐头的抗原绑定亲密关系被在房间从单个 cDNA 表示 VH 和 VL 区域的宫外的联盟者遗传上在大数量设计并且生产。由于它的更小的尺寸， scFv 分子表演在肿瘤穿入改进了 pharmacokinetics 并且被主人免疫系统更好容忍。

Monoclonal antibodies （mAb） have been successfully applied to the treatment of chronic diseases, such as cancer, inflammation and immune diseases. With the technical advances in antibody engineering, development of small recombinant antibody fragments as high affinity therapeutics with reduced immunogenicity has become under the spotlight. A popular format of the engineered recombinant antibody fragments is the single-chain fixed-variable （scFv） molecules, in which the VH and VL regions of the parental antibody are jointed together by a polypeptide linker. The scFv fragment retains the target specificity and antigenbinding affinity of the intact antibody, and can be genetically designed and produced in large quantity by ectopically expressing both VII and VL regions from a single cDNA in cells. Due to its smaller size, the scFv molecule shows improved pharmacokinetics in tumor penetration and is better tolerated by the host immune system. Despite these potential advantages of using scFv molecules for irnmunotherapy, especially for chronic diseases such as cancers, the treatment efficacy, however, is often compromised by the rapid blood clearance and insufficient concentration of the infused scFv fragments at the target site. To achieve high local concentrations in the target tissues, large amount of the recombinant scFv proteins （hundreds milligrams or more/a period of treatment） have to be administrated in the conventional antibody therapy. Thus, broad application of recombinant scFv antibody is limited by manufacturing difficulty and the high cost of production. To overcome these bottle-necks, Shi et al. [ 1] developed a promising therapeutic strategy by expressing in vivo scFv fragments of a mouse monoclonal antibody （AD5-10） that is directed against the TRAIL （tumor necrosis factor-related apoptosisinducing ligand） receptor DR5 （death receptor 5, also known as TRAIL receptor 2） [2], via recombinant adeno-associated virus （rAAV） vector-mediated antibody gene therapy.