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Blood, Vol. 94 No. 1 (July 1), 1999:
pp. 52-61
Engraftment of MDR1 and NeoR Gene-Transduced Hematopoietic
Cells After Breast Cancer Chemotherapy
Jeffrey A. Moscow,
Hui Huang,
Charles Carter,
Kenneth Hines,
JoAnne Zujewski,
Georgie Cusack,
Cathy Chow,
David Venzon,
Brian Sorrentino,
Yawen Chiang,
Barry Goldspiel,
Susan Leitman,
Elizabeth J. Read,
Andrea Abati,
Michael M. Gottesman,
Ira Pastan,
Stephanie Sellers,
Cynthia Dunbar, and
Kenneth H. Cowan
From the National Cancer Institute, National Heart, Lung and Blood
Institute, and the Clinical Center, National Institutes of Health,
Bethesda, MD; St Jude's Children Research Center, Memphis, TN; and
Genetic Therapy, Inc, a Novartis company, Gaithersburg, MD.
To determine whether the multidrug resistance gene MDR1
could act as a selectable marker in human subjects, we studied
engraftment of peripheral blood progenitor cells (PBPCs) transduced
with either MDR1 or the bacterial NeoR gene in six breast
cancer patients. This study differed from previous MDR1 gene
therapy studies in that patients received only PBPCs incubated in
retroviral supernatants (no nonmanipulated PBPCs were infused),
transduction of PBPCs was supported with autologous bone
marrow stroma without additional cytokines, and a control gene (NeoR)
was used for comparison with MDR1. Transduced PBPCs were
infused after high-dose alkylating agent therapy and before
chemotherapy with MDR-substrate drugs. We found that hematopoietic
reconstitution can occur using only PBPCs incubated ex vivo, that the
MDR1 gene product may play a role in engraftment, and that
chemotherapy may selectively expand MDR1 gene-transduced
hematopoietic cells relative to NeoR transduced cells in some patients.
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