PMID- 26871512 OWN - NLM STAT- MEDLINE DCOM- 20161109 LR - 20190221 IS - 2167-9436 (Electronic) IS - 2167-9436 (Linking) VI - 35 IP - 1 DP - 2016 Feb TI - Analysis of aDR5scFv with Specific Identification and Function. PG - 25-31 LID - 10.1089/mab.2015.0030 [doi] AB - 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. FAU - Cheng, Xiaofeng AU - Cheng X AD - 1 Radiotherapy Department, ChengGong Hospital, Xiamen University , Xiamen, Fujian, China . AD - 2 Center of Anti-Cancer Research, Medical College of Xiamen University , Xiamen, Fujian, China . FAU - Meng, Qingyu AU - Meng Q AD - 2 Center of Anti-Cancer Research, Medical College of Xiamen University , Xiamen, Fujian, China . FAU - Gao, Chunling AU - Gao C AD - 1 Radiotherapy Department, ChengGong Hospital, Xiamen University , Xiamen, Fujian, China . FAU - Zhuang, Guohong AU - Zhuang G AD - 2 Center of Anti-Cancer Research, Medical College of Xiamen University , Xiamen, Fujian, China . FAU - Huang, Xiaoping AU - Huang X AD - 2 Center of Anti-Cancer Research, Medical College of Xiamen University , Xiamen, Fujian, China . FAU - Zhang, Jiakai AU - Zhang J AD - 2 Center of Anti-Cancer Research, Medical College of Xiamen University , Xiamen, Fujian, China . FAU - Liu, Bin AU - Liu B AD - 2 Center of Anti-Cancer Research, Medical College of Xiamen University , Xiamen, Fujian, China . FAU - Fan, Xin AU - Fan X AD - 2 Center of Anti-Cancer Research, Medical College of Xiamen University , Xiamen, Fujian, China . FAU - Zhang, Minping AU - Zhang M AD - 2 Center of Anti-Cancer Research, Medical College of Xiamen University , Xiamen, Fujian, China . LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Monoclon Antib Immunodiagn Immunother JT - Monoclonal antibodies in immunodiagnosis and immunotherapy JID - 101590955 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antineoplastic Agents) RN - 0 (Immunoglobulin Variable Region) RN - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand) RN - 0 (Recombinant Proteins) RN - 0 (Single-Chain Antibodies) RN - 0 (TNFRSF10B protein, human) SB - IM MH - Adenocarcinoma/drug therapy/pathology/radiotherapy MH - Adenocarcinoma of Lung MH - Animals MH - Antibodies, Monoclonal/genetics/immunology/*pharmacology MH - Antineoplastic Agents/*pharmacology MH - Apoptosis/drug effects MH - Cell Line, Tumor MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Humans MH - Immunoglobulin Variable Region/genetics/immunology MH - Lung Neoplasms/drug therapy/pathology/radiotherapy MH - Mice, Nude MH - Receptors, TNF-Related Apoptosis-Inducing Ligand/*immunology MH - Recombinant Proteins/genetics/immunology/*pharmacology MH - Single-Chain Antibodies/genetics/immunology MH - Xenograft Model Antitumor Assays EDAT- 2016/02/13 06:00 MHDA- 2016/11/10 06:00 CRDT- 2016/02/13 06:00 PHST- 2016/02/13 06:00 [entrez] PHST- 2016/02/13 06:00 [pubmed] PHST- 2016/11/10 06:00 [medline] AID - 10.1089/mab.2015.0030 [doi] PST - ppublish SO - Monoclon Antib Immunodiagn Immunother. 2016 Feb;35(1):25-31. doi: 10.1089/mab.2015.0030.