Distinct experimental efficacy of anti-Fas/APO-1/CD95 receptor antibody in human tumors.
Ligation of the Fas receptor (FasR) is a key step in apoptosis induction. Using a series of human tumor cells (SNB19, SNB79, 143N2, and SHEP), we observed a distinct efficacy of human anti-FasR antibody with an apparent correlation with Fas cell surface antigen expression. In contrast, all cells studied expressed detectable FasR mRNA transcripts. For all anti-FasR antibody-sensitive tumor cells, we showed a similar efficacy of Mab according to dose fractionation and injection site. We showed that, when injected into nude mice bearing human osteosarcoma 143N2, neuroblastoma SHEP, prostatic cancer PAC120, and the two glioblastomas SNB19 and SNB79, anti-FasR Mab induces significant inhibition of the growth rate of 143N2, SHEP, and PAC120 tumors, but has no efficacy on SNB19 and SNB79 tumors, with a relationship between in vitro and in vivo sensitivity to anti-FasR antibody. Altogether, these results suggest the antitumor potential of anti-FasR antibody in human neoplasms.
Decaudin
D
D
Department of Hematology, Section de Recherche, UMR 147 CNRS, 75248 Paris Cedex 05, France. didier.decaudin@curie.net
Beurdeley-Thomas
A
A
Nemati
F
F
Miccoli
L
L
Pouillart
P
P
Bourgeois
Y
Y
Gonçalves
R B
RB
Rouillard
D
D
Poupon
M F
MF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000187:drug effects* / Q000235:genetics
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019014:fas Receptor