title: A recombinant adenovirus vector encoding the light chain of human coagulation factor VII and IgG1 Fc fragment to targeting tissue factor for colorectal cancer immunotherapy in the mouse model.
abstract: OBJECTIVE
  Over expression of tissue factor (TF) occurs in more than 50 % of colorectal cancer (CRC). Therefore, TF represents an attractive target antigen for immunotherapy in CRC.
  
  
  METHODS
  Here, we assessed the safety and efficacy of a recombinant adenovirus vector encoding the light chain of human coagulation factor VII (hfVII-LC) and human IgG1 Fc fragment (hIgG1-Fc), termed "benc vector," by targeting TF in the mouse model with colon cancer. Benc vector was administered intravenously or intratumorally in SCID mice with TF over-expressing HT-29 colon cancer. The safety and efficacy of benc vector were observed during animal experiments.
  
  
  RESULTS
  Complete inhibition of tumor growth (5/5) was observed not only in the intravenously injection of benc vector group but also in the intratumorally of benc vector group. We also observed a precautionary effect on lung metastases of HT-29 cells by intratumoral injection of benc vector. In the control group of animals given empty control vector, all animals (5/5) developed lung tumors and exhibited a higher number of nodules after injection with HT-29 cells via the tail vein. In contrast, only three animals (3/5) in the treatment group receiving benc vector had any observable lung metastases and a lower number of nodules. No animals died and no bleeding was observed both in treatment groups and control groups. Moreover, only moderate liver damage was detected in mice receiving benc vector by intravenous injections.
  
  
  CONCLUSIONS
  Benc vector encoding hfVII-LC and hIgG1-Fc can effectively inhibit tumor growth and metastases in SCID mice with TF over-expressing colon cancer and shows promise as an agent for CRC immunotherapy.
authors.affiliation: Department of Gastrointestinal Anal Surgery and Institute of Gastroenterology, The Third Affiliated Hospital, Nanchang University, Nanchang, 330008, China. benqiangrao@sina.com.cn
authors.forename: Benqiang
authors.initials: B
authors.lastname: Rao
authors.forename: Yuanhong
authors.initials: Y
authors.lastname: Gao
authors.forename: Qixu
authors.initials: Q
authors.lastname: Zhou
authors.forename: Pei
authors.initials: P
authors.lastname: Xiao
authors.forename: Shuang
authors.initials: S
authors.lastname: Xia
authors.forename: Jingsheng
authors.initials: J
authors.lastname: Ma
authors.forename: Juan
authors.initials: J
authors.lastname: Luo
authors.forename: Tao
authors.initials: T
authors.lastname: Xiao
authors.forename: Shilian
authors.initials: S
authors.lastname: Le
authors.forename: Meijin
authors.initials: M
authors.lastname: Huang
authors.forename: Jianping
authors.initials: J
authors.lastname: Wang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D005167:Factor VII / Q000235:genetics / Q000378:metabolism*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000378:metabolism*; D007074:Immunoglobulin G / Q000235:genetics; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods; D015552:Injections, Intralesional; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary / Q000628:therapy; D051379:Mice; D016513:Mice, SCID; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism*; D016896:Treatment Outcome; D047368:Tumor Burden / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D005167:Factor VII; D013925:Thromboplastin