Abstract
Our aim is to treat patients with B cell malignancies with radioimmunotherapy using monoclonal antibodies (mAb) such as CD19, CD20 and CD22. In this study we investigated the rate of internalization and catabolism of these mAb. After 24 h at 37°C, 20% – 25% of initially cell-bound 125I-CD19 mAb and 125I-CD22 mAb was degraded in B cells, whereas almost no degradation occurred after binding of 125I-CD20 mAb. For B cells expressing Fcγ receptor II (FcγRII), isotype-dependent degradation was noted as the CD19 IgG1 mAb showed an enhanced degradation rate compared to the switch variant IgG2a. The effect of various pharmaceutical agents that delay the internalization or subsequent degradation of mAb was evaluated. The degradation was inhibited most effectively by a combination of etoposide and vinblastine, resulting in accumulation of radioactivity in the target cell. Also the simultaneous application of CD20 or CD22 with 125I-CD19 mAb or of CD20 with 125I-CD22 mAb proved to be a potent inhibitor of the rapid degradation of these mAb, by inhibiting internalization via an FcγRII-mediated mechanism. Both methods of reducing the degradation of radioiodinated mAb are expected to prolong irradiation of malignant B cells and consequently result in an enhanced therapeutic effect in vivo.
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Received: 22 September 1995 / Accepted: 13 November 1995
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Vervoordeldonk, S., Balkenende, A., van den Berg, H. et al. Degradation of radioiodinated B cell monoclonal antibodies: inhibition via a FCγ -receptor-II-mediated mechanism and by drugs. Cancer Immunol Immunother 42, 24–30 (1996). https://doi.org/10.1007/s002620050247
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DOI: https://doi.org/10.1007/s002620050247