High level of MUC1 in serum of ovarian and breast cancer patients inhibits huHMFG-1 dependent cell-mediated cytotoxicity (ADCC).
The huHMFG-1 (AS1402) antibody is a humanised IgG1 directed against MUC1 and is currently in clinical trials for the treatment of breast carcinoma. Adenocarcinomas over-express and shed MUC1, and high MUC1 serum levels are associated with progressive disease. Here, we have investigated the effects of MUC1 present in sera from breast and ovarian cancer patients and that of NK cells on in vitro huHMFG-1-mediated ADCC, performed with and without the addition of various cytokines. Screening for patients with high levels of NK cells bearing the FcgammaRIIIa-158V polymorphism, adjusting the dosage to circulating levels of MUC1 and co-administration of NK cell activating cytokines may increase the efficacy of huHMFG-1 treatment.
Moreno
María
M
Department of Obstetrics and Gynaecology, VU Universiteit Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. M.Moreno@vumc.nl
Bontkes
Hetty J
HJ
Scheper
Rik J
RJ
Kenemans
Peter
P
Verheijen
René H M
RH
von Mensdorff-Pouilly
Silvia
S
D000230:Adenocarcinoma / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D000920:Antibody-Dependent Cell Cytotoxicity; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D018396:Mucin-1 / Q000097:blood* / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D011110:Polymorphism, Genetic
D000911:Antibodies, Monoclonal; D016207:Cytokines; C060192:MUC1 protein, human; D018396:Mucin-1; C469215:pemtumomab