Interferon-alpha conditioned sensitivity to an anti-epidermal growth factor receptor monoclonal antibody in a human lung cancer cell line with intermediate expression of the receptor.
Targeted therapy to the epidermal growth factor receptor (EGFR) seems to be related to its expression level on tumor cells. Interferon-alpha (IFN-alpha) induces growth inhibition but also may up-regulate the EGFR expression in some cancer cell lines. We aimed to determine whether the IFN-alpha combined with an EGFR-specific monoclonal antibody (nimotuzumab) may affect the growth of human tumor epithelial cell lines with different EGFR expression levels. H125, a lung adenosquamous carcinoma, and A431, a vulvar epidermoid carcinoma, cell lines express intermediate and high levels of EGFR, respectively, whereas MDA MB231, a breast adenocarcinoma cell line expresses undetectable levels of EGFR measured by flow cytometry/FACS. We found that IFN-alpha alone inhibited in a dose-dependent fashion the growth of all cell lines, but only up-regulated the EGFR expression in the lung carcinoma-derived cell line. Noteworthy, the combined treatment did not modify the complement-mediated cytotoxicity of the antibody although the antiproliferative activity of nimotuzumab in H125 cells in vitro increased when an IFN-alpha-conditioning treatment was used. In conclusion, this study may provide insights about the rational use of EGFR inhibitors into the immunopharmacological management of targeted therapies including the IFN-alpha for lung cancer.
Diaz
Arlhee
A
Department of Experimental Immunotherapy, Centre of Molecular Immunology, Havana, Cuba. arlhee@cim.sld.cu
Batista
Ana E
AE
Montero
Enrique
E
D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002469:Cell Separation; D003165:Complement System Proteins / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004306:Dose-Response Relationship, Immunologic; D004357:Drug Synergism; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006131:Growth Inhibitors / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D007167:Immunotherapy; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism*; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D014846:Vulvar Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D006131:Growth Inhibitors; D007155:Immunologic Factors; D016898:Interferon-alpha; C501466:nimotuzumab; D003165:Complement System Proteins; D066246:ErbB Receptors