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Distinct experimental efficacy of anti-Fas/APO-1/CD95 receptor antibody in human tumors
D Decaudin1, A Beurdeley-Thomas, F Nemati
1Department of Hematology, Section de Recherche, UMR 147 CNRS, 75248 Paris Cedex 05, France. didier.decaudin@curie.net
Abstract:
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.
Insights
Human anti-Fas receptor (FasR) antibodies show potential antitumor effects in various human neoplasms. Efficacy correlated with Fas cell surface antigen expression, suggesting targeted therapeutic strategies for cancer treatment.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Fas receptor (FasR) ligation is critical for initiating apoptosis.
- Understanding FasR's role in cancer is key for developing targeted therapies.
Purpose of the Study:
- To evaluate the antitumor efficacy of human anti-FasR antibody in human tumor cells.
- To correlate antibody efficacy with Fas cell surface antigen expression and FasR mRNA levels.
- To assess the in vivo efficacy of anti-FasR antibody in xenograft models.
Main Methods:
- In vitro assessment of anti-FasR antibody efficacy on human tumor cell lines (SNB19, SNB79, 143N2, SHEP).
- Analysis of Fas cell surface antigen expression and FasR mRNA transcripts.
- In vivo studies using nude mice bearing human tumor xenografts (osteosarcoma, neuroblastoma, prostatic cancer, glioblastomas).
Main Results:
- Anti-FasR antibody efficacy varied among tumor cells, correlating with Fas cell surface antigen expression.
- All tested cells expressed detectable FasR mRNA, but surface antigen levels differed.
- In vivo, the antibody significantly inhibited growth of osteosarcoma (143N2), neuroblastoma (SHEP), and prostatic cancer (PAC120) xenografts, but not glioblastomas (SNB19, SNB79).
Conclusions:
- Anti-FasR antibody demonstrates significant antitumor potential in specific human neoplasms.
- In vitro and in vivo sensitivity to the antibody is linked to Fas cell surface antigen expression.
- Results suggest targeted application of anti-FasR antibodies for effective cancer therapy.