Recombinant chimeric antibody hCAb as a novel anti-human colorectal carcinoma agent.
A new chimeric IgG1 antibody hCAb which could be specifically directed against a cell surface-associated glycoprotein of colorectal cancer cells was prepared by genetic engineering technology in our lab. In this study, we explored the potential therapeutic mechanisms and described the evaluation of hCAb directed against colorectal cancer. The standard 51Cr release assay showed that like many other clinically validated IgG1 monoclonal antibodies, hCAb primarily acts by antibody-dependent cell-mediated cytotoxicity (ADCC). The maximal cell lysis of ADCC induced by hCAb was over 50% in the presence of peripheral blood mononuclear cells (PBMCs). Moreover, in vivo studies showed potent antitumor effects in nude mice with SW480 and Hce-8693 tumor xenografts. The treatment with hCAb induced a dramatic reduction (over 70%) in tumor volume in comparison to untreated control group. Furthermore, during the period of treatment, the animals treated by hCAb did not show signs of wasting or other visible signs of toxicity. No obvious tissue damage in vital organs was detected. The chimeric antibody hCAb may be a promising candidate in the treatment of human colorectal cancer. This study can provide a reference for the potential application of hCAb in clinical trial.
Xiong
Hua
H
Cell Engineering Research Center, State Key Laboratory of Cancer Biology, Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an City, 710032, China.
Li
Ling
L
Liang
Qin-Chuan
QC
Bian
Hui-Jie
HJ
Tang
Juan
J
Zhang
Qin
Q
Mi
Li
L
Chen
Zhi-Nan
ZN
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification / Q000627:therapeutic use*; D000915:Antibody Affinity / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D001792:Blood Platelets / Q000166:cytology; D015153:Blotting, Western; D002452:Cell Count; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D007962:Leukocytes / Q000166:cytology; D051379:Mice; D008819:Mice, Nude; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000302:isolation & purification / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D011993:Recombinant Fusion Proteins