A
leukemia-selective
immunotoxin was constructed by linking recombinant
gelonin (rGel), a single chain ribosome inhibitory
protein, to recombinant humanized
M195 antibody (
HuM195), which recognizes the
cell-surface protein designated CD33. CD33 is an
antigen found on
myeloid leukemia blasts as well as myeloid progenitor cells but it is not expressed in detectable amounts on the ultimate hematopoietic progenitor stem cell. Our previous studies indicated that a non-recombinant humanized
immunotoxin displayed specific, potent toxicity towards CD33-positive cells but not to CD33-negative cells in vitro. In the current study, a recombinant humanized
immunotoxin,
HuM195-rGel, was evaluated in vivo in a nude mouse model of human
myeloid leukemias.
HuM195-rGel was found to target
leukemia cells rapidly in vivo and was subsequently internalized into the cells. For trials in vivo, nude mice were injected (ip) with 10(7) log-phase HL60 human
leukemia cells 10 days prior to the start of i.p.
HuM195-rGel treatments.
HuM195-rGel demonstrated significant
tumor suppressive activity in this model. While all mice treated with either saline, rGel alone, or
HuM195 plus unconjugated rGel (
at 10 or 14 days after
transplantation) had rapid
tumor growth or early deaths, 50% of mice treated with
HuM195-rGel failed to develop leukemic
tumors for 5 months and the 50% had significantly retarded
tumor growth
after treatment with
HuM195-rGel. Mice treated at later times (28 days after
transplantation of
leukemia cells) also showed delayed
leukemia cell growth, but no cures. These data show that
HuM195-rGel can target
leukemia cells in vivo and can result in pronounced anti-leukemic effects.