Antitumor xenograft activity with a conjugate of a Vinca derivative and the squamous carcinoma-reactive monoclonal antibody PF1/D

Cancer Res. 1987 Jun 15;47(12):3118-22.

Abstract

The human squamous carcinoma-reactive murine monoclonal antibody PF1/D was used to derive a conjugate with the Vinca derivative 4-desacetylvinblastine-3-carboxyhydrazide (PF1/D-DAVLBHYD). This immunoconjugate was shown to be largely aggregate free and there was no loss of immunoreactivity postconjugation. When tested in vivo in a 3-day-established human squamous carcinoma nude mouse xenograft model, the PF1/D-DAVLBHYD conjugate eliminated tumor growth with three injections (days 3, 6, and 9) at 2 mg/kg Vinca content. Significant tumor suppression was also observed with 0.5 mg/kg conjugate doses. In contrast, free PF1/D antibody had minimal antitumor activity and no activity was seen with identical doses of a control non-tumor-binding IgG-DAVLBHYD conjugate. Together, these data demonstrate the specificity of the PF1/D-DAVLBHYD antitumor effects.

MeSH terms

  • Animals
  • Antibodies, Monoclonal* / therapeutic use*
  • Carcinoma, Squamous Cell / immunology*
  • Cell Line
  • Chromatography, Gel
  • Humans
  • Immunotoxins / therapeutic use*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Transplantation, Heterologous
  • Vinblastine / analogs & derivatives*
  • Vinblastine / therapeutic use*

Substances

  • 4-desacetylvinblastine 3-carboxyhydrazide monoclonal antibody conjugates
  • Antibodies, Monoclonal
  • Immunotoxins
  • Vinblastine