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Purging of Mammary Carcinoma Cells During Ex Vivo Culture of
CD34+ Hematopoietic Progenitor Cells With Recombinant
Immunotoxins
A. Spyridonidis,
M. Schmidt,
W. Bernhardt,
A. Papadimitriou,
M. Azemar,
W. Wels,
B. Groner, and
R. Henschler
From the Department of Hematology/Oncology, University Medical
Center, Freiburg; and Institute for Experimental Cancer Research, Tumor
Biology Center, Freiburg, Germany.
Tumor cells have been found in autologous hematopoietic cell
transplants used after high-dose chemotherapy. To specifically eliminate contaminating mammary tumor cells during ex vivo expansion of
CD34+ hematopoietic progenitor cells, we used recombinant
immunotoxins (ITs) directed against cell-surface antigens expressed on
mammary carcinoma cells. ITs were expressed from fusion cDNAs combining a single-chain antibody fragment (scFv) directed against the Erb-B2 or
epidermal growth factor (EGF) receptors with a truncated
Pseudomonas exotoxin A fragment devoid of its cell-binding
domain. CD34+ hematopoietic progenitor cells did not
express Erb-B2 and EGF receptors as detected by Western blotting. Ex
vivo expansion of total hematopoietic cells or of colony-forming cells
from CD34+ progenitors in the presence of stem-cell
factor (SCF), interleukin-1 (IL-1), IL-3, IL-6, and erythropoietin
(Epo) was not affected when ITs were added to the cultures. In
contrast, MDA-MB 453 and MCF-7 mammary carcinoma cells were depleted in
a dose- and time-dependent manner by more than 3 log in coculture with
CD34+ cells over a period of 7 days in the presence of
100 to 1,000 ng/mL of anti-Erb-B2 IT. This included elimination of the
subpopulations with regrowth potential. Similarly, addition of either
anti-Erb-B2 or anti-EGF receptor ITs to primary breast cancer cells
isolated from patients with metastatic disease resulted in elimination of cytokeratin-positive cells in seven of seven samples. ITs are highly
efficient and convenient to use for the depletion of mammary tumor
cells during ex vivo expansion of hematopoietic progenitor-cell autografts.
Blood, Vol. 91 No. 5 (March 1), 1998:
pp. 1820-1827
© 1998 by The American Society of Hematology.
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