Abstract
Myeloid cells can mediate tumor cell cytotoxicity via certain receptors for immunoglobulins. Among the different Fc receptors, the high-affinity IgG receptor (Fc gamma RI, CD64) is a promising trigger molecule because it is selectively expressed on effector cells, including monocytes/macrophages and granulocyte colony-stimulating factor (G-CSF)-primed neutrophils. In vitro, a bispecific antibody (BsAb) (MDX-210, constructed by chemically cross-linking F(ab') fragments of monoclonal antibody (mAb) 520C9 to HER-2/neu and F(ab') fragments of mAb 22 to Fc gamma RI) mediated effective lysis of HER-2/neu overexpressing breast cancer cell lines. HER-2/neu (c-erbB2) is overexpressed in approximately 30% of breast and ovarian carcinomas and is a target for immunotherapy in clinical trials. In vitro assays showed Fc gamma RI-positive neutrophils to constitute a major effector cell population during G-CSF therapy. Based on these preclinical data and a preceding study at Dartmouth (New Hampshire) with a single dose of MDX-210 alone, a combination of G-CSF and MDX-210 is tested in a phase I study in breast cancer patients. In this study, patients receiving G-CSF are treated with escalating single doses of MDX-210. This therapy was generally...Continue Reading
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