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FM Uckun, LM Chelstrom, JD Irvin, D Finnegan, R Gunther, J Young, V Kuebelbeck, DE Myers and LL Houston
Department of Therapeutic Radiology-Radiation Oncology, University of
Minnesota Health Sciences Center, Minneapolis.
We show that a highly aggressive subclone of murine BCL-1 B-lineage
leukemia expresses a single 2.4-kb transcript hybridizing to the human CD19
cDNA probe and reacts strongly with the anti-human CD19 monoclonal
antibodies (MoAb) B43, B4, Leu-12, and J3-119. In contrast to their strong
reactivity with anti-human CD19 MoAb, BCL-1 cells show no reactivity with
MoAb directed against human CD22, CD72, HLA-DR, IgD, or IgM. Western blot
analysis of BCL-1 whole cell lysates with the anti- human CD19 MoAb J3-119
showed a single 69-Kd protein band, which was not detected by the negative
control MoAb G19.4 (anti-CD3). In contrast to BCL-1 cells, normal BALB/c
splenocytes or mouse splenocyte/myeloma hybridoma cell lines did not (1)
express any transcripts that hybridized to the human CD19 cDNA probe, (2)
react with B43/anti-CD19 MoAb, or (3) express the 69-Kd protein that reacts
with the anti-human CD19 MoAb J3-119. Murine BCL-1 B-cell leukemia thus
provides a unique model of disseminated B-lineage leukemia to evaluate the
antileukemic efficacy of anti-CD19 immunotoxins. This model was
subsequently used to evaluate the in vivo homing ability, pharmacokinetics,
and antileukemic efficacy of B43 MoAb conjugated to the plant hemitoxin
pokeweed antiviral protein (PAP). B43-PAP immunotoxin (1) showed strong and
antigen-specific reactivity with BCL-1 cells, (2) promptly penetrated the
spleens of leukemic mice, (3) rapidly reduced the BCL-1 leukemia burden of
leukemic mice and, most importantly, (4) improved survival. Finally,
B43-PAP immunotoxin was more effective against BCL-1 leukemia than 700 cGy
(LD100/30) total body irradiation (TBI) followed by syngeneic bone marrow
transplantation (BMT).
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| Copyright © 1992 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||