In vitro and in vivo stability and anti-tumour efficacy of an anti-EGFR/anti-CD3 F(ab')2 bispecific monoclonal antibody

D. R M Negri, E. Tosi, O. Valota, S. Ferrini, A. Cambiaggi, S. Sforzini, A. Silvani, P. A. Ruffini, M. I. Colnaghi, S. Canevari

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Abstract

The in vitro and in vivo stability and anti-tumour efficacy of the anti-EGFR/anti-CD3 bispecific monoclonal antibody (biMAb), M26.1, were analysed. The interaction of the intact biMAb with Fc receptor I (FcγRI) present on human leucocytes was not observed when the antibody was used as an F(ab')2 fragment. A CD8+ T-cell clone coated with M26.1 F(ab')2 was as effective as the intact biMAb in inducing IGROV1 target cell lysis when tested in a 51Cr-release assay. Variable levels of reduction of F(ab')2 to monovalent F(ab') were observed upon incubation with human ovarian cancer ascitic fluid (OCAF) or with human glioblastoma cavity fluid (GCF), but not with mouse or human sera. Activated lymphocytes coated with F(ab')2 and incubated in vitro with GCF or OCAF for 24 and 48 h respectively maintained their targeting. Thus, the F(ab')2, when present as a soluble molecule, but not when bound to T cells, might lose some functional activity as a consequence of partial reduction to F(ab'). In normal mice, M26.1 F(ab')2 retained full cytotoxic activity in the circulation, and clearance values were similar to those obtained with parental and other MAb F(ab')2. Treatment of IGROV1 tumour-bearing mice with activated human lymphocytes coated with the M26.1 F(ab')2 significantly prolonged survival of the animals compared with tumour-bearing untreated and control mice treated with lymphocytes or F(ab')2 alone. Together, these results suggest the clinical usefulness of bispecific M26.1 F(ab')2 as a targeting agent for local treatment of tumours such as glioma and ovarian cancers that express variable levels of epidermal growth factor receptor (EGFR).

Original languageEnglish
Pages (from-to)928-933
Number of pages6
JournalBritish Journal of Cancer
Volume72
Issue number4
Publication statusPublished - 1995

Keywords

  • Bispecific monoclonal antibody
  • Epidermal growth factor receptor
  • Locoregional immunotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Negri, D. R. M., Tosi, E., Valota, O., Ferrini, S., Cambiaggi, A., Sforzini, S., Silvani, A., Ruffini, P. A., Colnaghi, M. I., & Canevari, S. (1995). In vitro and in vivo stability and anti-tumour efficacy of an anti-EGFR/anti-CD3 F(ab')2 bispecific monoclonal antibody. British Journal of Cancer, 72(4), 928-933.