Table 1

CD19 and CD21 expression levels and cytotoxicity of hBU12 -vcMMAE against ALL, CLL, and NHL tumor cell lines grown in culture

Tumor type / cell lineCD21, copy no.CD19, copy no.IC50, nM hBU12-vcMMAEIC50, nM free MMAE
ALL
    Nalm-60537734.0 ± 0.050.65 ± 0.07
    RS4;110382270.050 ± 0.0070.080 ± 0.007
Transformed follicular lymphoma
    DOHH20400564.5 ± 0.70.200 ± 0.005
    WSU-NHL0362420.35 ± 0.070.200 ± 0.005
DLBCL
    HT952368340.20 ± 0.040.103 ± 0.002
    RL032542> 3000.25 ± 0.07
    WSU-DLCL201992451 ± 0.710.30 ± 0.01
    SUDHL-60137840.04 ± 0.010.136 ± 0.003
    SUDHL-403893299 ± 150.71 ± 0.07
Burkitt
    CA462167572401.4 ± 0.80.53 ± 0.09
    Namalwa3742862945 ± 290.31 ± 0.10
    Ramos2369410160.60 ± 0.280.15 ± 0.01
    Daudi255315407430 ± 20.193 ± 0.007
    Raji566607879833.3 ± 7.10.43 ± 0.06
Large B-cell lymphoma
    ARH-772953754324126 ± 310.63 ± 0.16
CLL
    MEC-23324667562> 3002 ± 0.6
    JVM3178502632142 ± 50.20 ± 0.07
T-cell leukemia
    Jurkat: CD19> 3000> 3000.25 ± 0.04
  • IC50 values were determined by incubation of the tumor cell lines for 96 hours to the hBU12-vcMMAE conjugate or MMAE, as indicated. Cell lines, in which less than 50% cytotoxicity was achieved at concentrations greater than or equal to 300 nM, were considered nonresponsive. Both unconjugated hBU12 and a control, nonbinding vcMMAE conjugate exhibited negligible antitumor activities against these cell lines. All values obtained for hBU12-vcMMAE are significantly different from control-vcMMAE compounds tested in the same assay (Student t test, data not shown). Jurkat cells were used as a CD19 control cell line. The absence of activity of hBU12-vcMMAE on these control cells suggested that the antitumor activity is immunologically specific. Data shown represent the mean plus or minus SD of three replicates from 2 independent experiments.