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Minor human antibody response to a mouse and chimeric monoclonal antibody after a single i.v. infusion in ovarian carcinoma patients: a comparison of five assays

  • Original Article
  • Human Anti-(Mouse lg), Chimeric Antibody, Double-Antigen Assay
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Abstract

The human anti-(mouse Ig) antibody (HAMA) response was measured in serum of 52 patients suspected of having ovarian carcinoma who had received an i.v. injection of either the murine monoclonal antibody (mAb) OV-TL 3 F(ab′)2 (n=28, 1 mg) or the chimeric mouse/human mAb MOv18 (cMOv18;n=24, 3 mg). Serum samples were taken before injection and 2–3 and 6–14 weeks after administration. A double-antigen or bridging assay was developed to detect responses against both murine as well as chimeric antibodies. In addition, an indirect enzyme-linked immunosorbent assay (ELISA) as well as three commercially available assays were used to study antibody response against the murine antibody OV-TL 3. With both the double-antigen (bridging) assay and the indirect ELISA 1 of the 28 patients (4%) injected with murine OV-TL 3 F(ab′)2 showed a HAMA reaction 6 weeks after injection, which was demonstrated to be a mixed anti-isotypic and anti-idiotypic response. None of the 24 patients injected with the chimeric MOv18 showed an anti-chimeric antibody response. The various commercially available assays demonstrated conflicting results. The double-antigen-or bridging assay is a reliable method to detect anti-murine and antichimeric antibodies. The assay can be easily adapted for use with human antibodies. The immunogenicity of OV-TL 3 F(ab′)2 and cMOv18 in patients is low, making both antibodies candidates for immunotherapy.

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Authors and Affiliations

  1. Departments of Obstetrics and Gynaecology, Free University Hospital, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands

    Marrije R. Buist & Peter Kenemans

  2. Department of Clinical Chemistry, Free University Hospital, Amsterdam, The Netherlands

    Gerard J. van Kamp

  3. Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands

    Hidde J. Haisma

Authors
  1. Marrije R. Buist
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  2. Peter Kenemans
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  3. Gerard J. van Kamp
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  4. Hidde J. Haisma
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Additional information

This work was supported by a clinical research grant of the Netherlands Organization for Scientific Research (NWO 900-716-020) and by the Biocare Foundation (grant 92-05).

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Buist, M.R., Kenemans, P., van Kamp, G.J. et al. Minor human antibody response to a mouse and chimeric monoclonal antibody after a single i.v. infusion in ovarian carcinoma patients: a comparison of five assays. Cancer Immunol Immunother 40, 24–30 (1995). https://doi.org/10.1007/BF01517232

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  • DOI: https://doi.org/10.1007/BF01517232

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