title: Analysis of aDR5scFv with Specific Identification and Function.
abstract: Death receptor 5 (DR5) can selectively induce cell death in a wide variety of tumor cells. However, at least certain versions of the recombinant soluble TRAIL (sTRAIL) or anti-DR5 monoclonal antibody (mAb) are also shown to cause apoptosis in normal cells (especially in hepatocytes), hampering its clinical use for cancer therapy. Recently, the development of small recombinant antibody fragments as high-affinity therapeutic reagents with reduced immunogenicity has come under the spotlight. A popular format of engineered recombinant antibody fragment is the single-chain fixed-variable (scFv) molecule, in which the VH and VL regions of the parental antibody are joined by a polypeptide linker. The scFv fragment retains the target specificity and antigen binding affinity of the intact antibody, whereas it can be genetically designed and produced in large quantities by ectopically expressing both VH and VL regions from a single cDNA in cells. In this study, an aDR5scFv was constructed and expressed, and it was conformed so that it could recognize and bind eDR5 specifically. The therapeutic effects on human lung adenocarcinoma cells lines 973 in vitro and in vivo were detected by MTT assay, flow cytometry, hematoxylin and eosin staining, and TUNEL assay. aDR5scFv was able to induce 973 cell apoptosis in an in vitro system. The protein expressions of caspase-3, Bax, and cytochrome c were raised, and aDR5scFv also inhibited tumor growth in mice with its effect as well as with radiotherapy. It is concluded that aDR5scFv could possibly be considered as a novel therapeutic candidate for the treatment of tumors.
authors.affiliation: 1 Radiotherapy Department, ChengGong Hospital, Xiamen University , Xiamen, Fujian, China .|2 Center of Anti-Cancer Research, Medical College of Xiamen University , Xiamen, Fujian, China .
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Cheng
authors.affiliation: 2 Center of Anti-Cancer Research, Medical College of Xiamen University , Xiamen, Fujian, China .
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Meng
authors.affiliation: 1 Radiotherapy Department, ChengGong Hospital, Xiamen University , Xiamen, Fujian, China .
authors.forename: Chunling
authors.initials: C
authors.lastname: Gao
authors.affiliation: 2 Center of Anti-Cancer Research, Medical College of Xiamen University , Xiamen, Fujian, China .
authors.forename: Guohong
authors.initials: G
authors.lastname: Zhuang
authors.affiliation: 2 Center of Anti-Cancer Research, Medical College of Xiamen University , Xiamen, Fujian, China .
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Huang
authors.affiliation: 2 Center of Anti-Cancer Research, Medical College of Xiamen University , Xiamen, Fujian, China .
authors.forename: Jiakai
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 2 Center of Anti-Cancer Research, Medical College of Xiamen University , Xiamen, Fujian, China .
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: 2 Center of Anti-Cancer Research, Medical College of Xiamen University , Xiamen, Fujian, China .
authors.forename: Xin
authors.initials: X
authors.lastname: Fan
authors.affiliation: 2 Center of Anti-Cancer Research, Medical College of Xiamen University , Xiamen, Fujian, China .
authors.forename: Minping
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D000077192:Adenocarcinoma of Lung; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D008819:Mice, Nude; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D057127:Single-Chain Antibodies / Q000235:genetics / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007135:Immunoglobulin Variable Region; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D011994:Recombinant Proteins; D057127:Single-Chain Antibodies; C505639:TNFRSF10B protein, human