Antitumor xenograft activity with a conjugate of a Vinca derivative and the squamous carcinoma-reactive monoclonal antibody PF1/D.
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.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D002460:Cell Line; D002850:Chromatography, Gel; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014183:Transplantation, Heterologous; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000627:therapeutic use*
C052672:4-desacetylvinblastine 3-carboxyhydrazide monoclonal antibody conjugates; D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D014747:Vinblastine