Inhibition of tumour growth and metastasis of human fibrosarcoma cells HT-1080 by monoclonal antibody BCD-F9.
BCD-F9 is a murine IgG(2a) monoclonal antibody (mAb) that recognises a conformational epitope found on the surface of many human tumour cells. The aim of this study was to investigate the ability of BCD-F9 to recognise a variety of neoplastic cell lines and to test BCD-F9 in vivo for anticancer activity in subcutaneous (s.c.) and metastatic tumour models. Intravenous (i.v.) administration of BCD-F9 in CD-1 nude mice xenografted s.c. with human HT-1080 cells led to a significant inhibition of tumour growth. We demonstrated that BCD-F9 administrated i.v. significantly prolonged the life-span of CD-1 nude mice inoculated i.v. with the same tumour cell line that induces aggressive lung metastases in the untreated mice. We also investigated the antitumour activity of BCD-F9 in vitro in antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent complement-mediated cytotoxicity (ADCMC) assays. The effector cell subpopulations were obtained by macrophage stimulation (thioglycollate) or natural killer (NK) cell enrichment (negative selection). BCD-F9 was found to be effective in mediating tumour cell killing in vitro by ADCC and ADCMC mechanisms. These results suggest that the mAb BCD-F9 can have a potential use in immunotherapy for treatment of tumours of different origin.
Popkov
M
M
INRS-Institut Armand-Frappier, University of Quebec, 531 Blvd. des Prairies, Laval, Quebec, Canada H7V 1B7.
Sidrac-Ghali
S
S
Lusignan
Y
Y
Lemieux
S
S
Mandeville
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D002455:Cell Division; D005260:Female; D005354:Fibrosarcoma / Q000473:pathology / Q000628:therapy*; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured; D014611:Vaccination / Q000379:methods
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D007074:Immunoglobulin G