PART m-c 
Scientific Abstract 
SCIENTIFIC ABSTRACT 
Replication incompetent, recombination incompetent retroviral vectors will be used to introduce 
chemotherapy resistance (MDR-1) cDNAs into the normal stem cells of autologous peripheral 
blood removed and stored following chemotherapy delivered to patients with breast cancer who 
are poor risk, and therefore at very high risk (80%) of dying of their disease. We estimate that 
between 0.6 and 2 x 10^ CD34 positive cells/kg will be infused and that among these, 50% of 
the total CD34 selected cells infused will be exposed to a MDR-1 containing vector. We will 
look for the number of MDR-1 marked cells using a methylcellulose late progenitor colony 
culture system and a PCR assay for the MDR-1 gene. In addition, we will monitor the 
acquisition of chemotherapy resistance by stem cells of varying degrees of immaturity by using 
culture assays for these cells under chemotherapy selection (methylcellulose assay and colonies 
grown from Dexter cultures incubated for more than 35 days using PCR for MDR-1. These 
studies will help us evaluate if introduction of MDR-1 cDNA into peripheral blood will confer 
chemotherapy resistance on these cells, thus allowing therapy of a greater level of intensity of 
taxol to be delivered following transplant and therefore change the course of poor prognosis 
breast cancer in these patients. 
Recombinant DNA Research, Volume 19 
[517] 
