Table II.

Comparison of mIgG1 and mIgG2a anti-DR4 mAbs

IsotypeEpitopeamAbBlocking ActivityIn vitrob Apoptosis% Tumor Growth Inhibitionc (p value)
3G1IgG1C40+/−42 (0.13)
4E7IgG1B22+++76 (0.03)
4H6IgG1A5++++++99 (<0.01)
4H6dIgG2aA3.5++++++23 (0.7)
1H5IgG2aA4++++++26 (0.45)
4G7IgG2aB120+++19 (0.46)
  • a The epitope was designated arbitrary based on results obtained from competitive binding ELISA using biotinylated mAbs.

  • b In vitro apoptotic activity of mAbs (1 μg/ml) was determined using SK-MES-1 cells in the presence of goat anti-mouse IgG. +++, >90% killing; +/−, <30% killing.

  • c Nude mice bearing Colo 205 xenografts were treated with mAbs at 2.5 mg/kg, twice per week, starting on day 4. On day 22, tumor sizes were measured and the percentage of growth inhibition was calculated. Tumor sizes (mean ± SEM) of PBS- and mAb 4H6-treated groups were 495 ± 139 and 2 ± 2 mm3, respectively. Each group consists of seven to eight mice. Statistical p values were obtained by comparison with the PBS control group.

  • d The mAb 4H6* is an IgG2a isotype variant of the parent IgG1-4H6 mAb.