Human recombinant anti-thyroperoxidase autoantibodies: in vitro cytotoxic activity on papillary thyroid cancer expressing TPO.
BACKGROUND
Thyroid cancers are difficult to treat due to their limited responsiveness to chemo- and radiotherapy. There is thus a great interest in and a need for alternative therapeutic approaches.


RESULTS
We studied the cytotoxic activity of anti-thyroperoxidase autoantibodies (anti-TPO aAbs, expressed in baculovirus/insect cell (B4) and CHO cells (B4') or purified from patients' sera) against a papillary thyroid cancer (NPA) cell line. Anti-TPO aAbs from patients' sera led to a partial destruction of NPA cell line by complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) and exhibited an anti-proliferative activity. Comparison of the cytotoxic activity of anti-TPO aAbs shows that B4' induced an anti-proliferative effect and a better ADCC than B4, but a lower one than anti-TPO aAbs from patients' sera. Antibody-dependent cell-mediated cytotoxicity was increased when human peripheral blood mononuclear cells were used as effector cells, suggesting that FcgammaRs, CD64, CD32 and CD16 are involved. Indeed, anti-TPO aAbs from patients' sera, but not B4 and B4', exhibited CDC activity.


CONCLUSIONS
These data indicate that anti-TPO aAbs display moderate ADCC and anti-proliferative activities on NPA cells; IgG glycosylation appears to be important for cytotoxic activity and ADCC efficiency depends on FcgammaR-bearing cells. Finally, recombinant human anti-TPO aAbs cannot yet be considered as an optimal tool for the development of a novel therapeutic approach for thyroid cancer.
Centre National de la Recherche Scientifique-UMR 5232, CPID, Faculté de Pharmacie, 15 avenue Charles Flahault, Montpellier Cedex 5, France.
S A
SA
Rebuffat
M
M
Morin
B
B
Nguyen
F
F
Castex
B
B
Robert
S
S
Péraldi-Roux
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D001323:Autoantibodies / Q000276:immunology / Q000494:pharmacology*; D001324:Autoantigens / Q000276:immunology*; D016466:CHO Cells; D002291:Carcinoma, Papillary / Q000276:immunology / Q000473:pathology*; D049109:Cell Proliferation; D015922:Complement C1q / Q000276:immunology; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007453:Iodide Peroxidase / Q000276:immunology*; D033862:Iron-Binding Proteins / Q000276:immunology*; D013964:Thyroid Neoplasms / Q000276:immunology / Q000473:pathology*; D014407:Tumor Cells, Cultured; D006023:Glycoproteins
D001323:Autoantibodies; D001324:Autoantigens; D015922:Complement C1q; D007074:Immunoglobulin G; D007453:Iodide Peroxidase; D033862:Iron-Binding Proteins; C046179:glycosylated IgG; D006023:Glycoproteins; C056658:TPO protein, human