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Retroviral gene transduction of adult peripheral blood or marrow- derived
CD34+ cells for six hours without growth factors or on autologous stroma
does not improve marking efficiency assessed in vivo
RV Emmons, S Doren, J Zujewski, M Cottler-Fox, CS Carter, K Hines, JA O'Shaughnessy, SF Leitman, JJ Greenblatt, K Cowan and CE Dunbar
Hematology Branch, National Heart, Lung and Blood Institute, National
Institutes of Health, Bethesda, MD, USA.
Our previous work in patients undergoing autologous transplant for multiple
myeloma (MM) or breast cancer (BC) has shown that retroviral transduction
of adult CD34+ cells for 72 hours in the presence of interleukin-3 (IL-3),
IL-6, and stem cell factor (SCF) resulted in .01% to 1% long-term marking
of peripheral blood and marrow cells (Blood 85:3948, 1995). In this study
we compare these previous studies to transduction with no added growth
factors, previously shown to result in higher levels of marking in children
(Lancet 342:1134, 1993) or transduction in the presence of an autologous
stromal layer. Peripheral blood (PB) mononuclear cells were collected via
apheresis after high- dose cyclophosphamide and granulocyte
colony-stimulating factor. Bone marrow (BM) was also harvested in all
patients. One third of both BM and PB collections were enriched for CD34+
cells and transduced with one of two marking vectors containing the
neomycin-resistance gene to distinguish cells originating from BM and PB
posttransplantation. Cells from 3 MM and 2 BC patients were transduced
without growth factors for 6 hours and cells from 2 MM and 2 BC patients
were transduced in the presence of autologous marrow stroma. Immediately
posttransduction, the percentage of Neo-resistant PB and BM progenitors
(colony-forming units) were: 0% to 19% in the 6-hour no growth factor group
and 0% to 36% in the autologous stroma group. After conditioning therapy,
both transduced and untransduced PB and BM fractions were infused into the
patients. Semi-quantitative nested DNA polymerase chain reaction was
performed on total, mononuclear, and granulocyte fractions of PB and BM at
1, 3, 6, 9, 12, and 18 months. Poor marking has been observed in both
groups, with no consistently positive patients. These results compare
unfavorably with our prior experience using growth factors during
transduction. Further optimization of transduction conditions and vectors
needs to be developed to improve transduction efficiency of adult human
repopulating hematopoietic cells.
Volume 89,
Issue 11,
pp. 4040-4046,
06/01/1997
Copyright © 1997 by The American Society of Hematology
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