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  • Title: Preclinical studies combining bispecific antibodies with cytokine-stimulated effector cells for immunotherapy of renal cell carcinoma.
    Author: Elsässer D, Stadick H, Stark S, Van de Winkel JG, Gramatzki M, Schrott KM, Valerius T, Schafhauser W.
    Journal: Anticancer Res; 1999; 19(2C):1525-8. PubMed ID: 10365137.
    Abstract:
    BACKGROUND: Bispecific antibodies--consisting of a F(ab')-fragment derived from a monoclonal antibody against a tumor epitope as well as of another antibody against a cytotoxic trigger molecule on immune effector cells--can improve the effectiveness of antibody-based tumor therapy. MATERIALS AND METHODS: We used bispecific antibodies with one specifity against the EGF-receptor, which is overexpressed on the majority of renal cell carcinomas, and another specifity against Fc receptors on human leukocytes (Fc gamma RI/CD64; Fc gamma RIII/CD16 and Fc alpha RI/CD89). As source of effector cells, whole blood from patients treated with G-CSF, GM-CSF or IL2/IFN-alpha was used in 51Cr- release assays using various renal cancer cell lines as tumor targets. Further experiments with Percoll-isolated granulocytes or mononuclear cells from the same donors were performed in order to identify the active effector cell populations. RESULTS: Compared with conventional monoclonal EGF-R directed antibodies (murine IgG2a, humanized IgG1), bispecific antibodies induced significantly enhanced cytotoxicity. Highest amounts of tumor cell killing were observed using whole blood from patients treated with G-CSF or GM-CSF in combination with an [Fc alpha RI x EGF-R] bispecific antibody. Under these conditions, granulocytes constituted the most active effector cell population. CONCLUSION: The combination of myeloid growth factors and bispecific antibodies offer a promising new approach for the treatment of advanced renal cell carcinoma.
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