Estradiol metabolism: An endocrine biomarker for chemoprevention of human mammary carcinogenesis
✍ Scribed by Nitin T. Telang; H. Leon Bradlow; Michael P. Osborne
- Book ID
- 102303299
- Publisher
- John Wiley and Sons
- Year
- 1993
- Tongue
- English
- Weight
- 94 KB
- Volume
- 53
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Poster Abstracts ligand binding site and thus should not be blocked in viuo by the relatively high levels of human IgG. Her-2/neu is overexpressed in human breast carcinomas with poor prognosis. In vitro studies with MDX-210 have shown effective killing of tumor cell lines that express the HER-2/neu antigen. Elght patients have been treated to date. The dosage levels tested to date are 0.35,1.0, and 3.5 mg/m2 infused intravenously at 6.0 mg/hour. Infusion of MDX-210 has been well-tolerated by all patients. The principal toxicities have been Grade 1/11 fevers and malaise that have fully resolved by 12 hours post infusion. Evidence of immunological activity has been observed even at the lowest dose tested. Plasma tumor necrosis factor alpha (TNFa) increased to as high as 500 picogram/ml in 5 of 6 patients tested. Peripheral blood monocytopenia, either preceding or concurrent with elevations of plasma TNFa, is consistent with binding of MDX-210 to both immune effector cells and target breast tumor cells.
Significant dose-dependent in v i m binding of MDX-210 to CD 64 has been observed for more than 24 hours post infusion. It has been demonstrated in cell culture studies that MDX-210 triggers release of TNFa from immune effector cells in the presence, but not in the absence, of target tumor cells. The observation that MDX-210 is immunologically active at non-toxic doses forms the basis for considering MDX-210 as a candidate chemotherapeutic drug for recurrent or secondary breast cancers.