Anti-tumor activity of monoclonal antibody CIBCNSH3 generated to the human EGF receptor.
The overexpression of the human epidermal growth factor receptor (EGFR) has been demonstrated in many malignancies like squamous cell carcinoma of the head and neck, cervix, breast etc. which are most prevalent in India. This is often associated with poor prognosis and high mortality in these patients. Monoclonal antibodies generated against EGFR which inhibit binding of ligands like EGF to their receptor have anti-tumor activity and hence therapeutic application. One such monoclonal antibody designated as CIBCNSH3 generated in our laboratory has been found to recognize an epitope in the extracellular domain of EGFR by immunoprecipitation. By immunoperoxidase test this antibody exhibited strong reactivity to EGFR in head and neck cancers and breast cancers studied. It also inhibited the binding of Epidermal Growth Factor (EGF) to its receptor on MDA MB468 breast cancer cells rich in EGFR as revealed by competitive binding assay using 125I EGF, indicating its anti-tumor activity. The in vivo therapeutic efficacy has been demonstrated by injecting i.p. into tumor bearing mice 200 micrograms of the antibody for 4 consecutive days and then 100 micrograms twice a week resulting in complete regression of tumors of initial tumor size of 0.5-1.0 cm diameter. These results were compared with a control antibody against EGFR and also a nonspecific antibody which were administered to different groups of animals. In vivo studies performed using cell lines in culture like MDA MB468, MDA MB157 and HN5 with overexpression of EGFR revealed 98% cell death when incubated with different concentrations of the antibody. This monoclonal antibody seems to have a promising future application as therapeutic agent for tumors which overexpress EGFR.
Udayachander
M
M
Department of Biochemical Oncology, Cancer Institute (WIA), Madras, India.
Dean
C J
CJ
Meenakshi
A N
AN
Sivakumar
N
N
Babu
P B
PB
Sivakumar
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000473:pathology; D002277:Carcinoma / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004815:Epidermal Growth Factor / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D066246:ErbB Receptors / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology; D006801:Humans; D007116:Immunization, Passive; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D009101:Multiple Myeloma / Q000473:pathology; D009363:Neoplasm Proteins / Q000276:immunology*; D016719:Radioimmunodetection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000939:Epitopes; D009363:Neoplasm Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors