Recombinant DNA Advisory Committee - 03/1-2/93 
of these cells express the MDR gene. In addition, the investigators have not stated the 
length of time that they expect to observe gene expression in these patients. How long 
will patients have to be followed after ABM transplantation to demonstrate the presence 
of resistant colonies and PCR positive cells, which is indicative of transduced committed 
progenitors? 
The administration of Taxol is another aspect of this protocol that should be considered 
by the RAC. Taxol is not routinely administered following ABM for breast cancer at 
Columbia University. Since the administration of Taxol is a procedure that is not 
independent of the gene transfer procedure, then the committee has a responsibility to 
review all aspects of the protocol. Dr. Parkman stated that his written review asked if 
patients tolerated 175 milligrams per meter squared (mg/m 2 ) of Taxol 50 days following 
ABM transplantation. The investigators responded that one patient had received this 
dose of Taxol, 175 mg/m 2 ; however, the drug was administered on day 90 instead of day 
50. He stated that data obtained from 1 patient treated on day 90 following ABM does 
not justify the treatment of many patients on day 50 following ABM. 
Dr. Parkman summarized the questions that the investigators should respond to during 
their oral presentation: (1) Is there preclinical data demonstrating gene transduction 
into immature hematopoietic progenitors as opposed to committed progenitors? (2) 
What are the endpoints of the study? and (3) Is there any additional clinical data 
regarding the safety of Taxol administration at the dose proposed for this study? 
Review-Dr. Krogstad 
Dr. Krogstad stated that the investigators had responded adequately to his concern about 
the use of the term MDR-1 for both the genomic DNA message and the gene product. 
It is unclear how gene expression resulting from the transduced gene will be 
distinguished from the natural expression of MDR from genomic DNA. Since 1 of the 
objectives of this study is to select for MDR-1 producing cells or cells that exhibit greater 
levels of p-glycoprotein, the investigators should provide further clarification on this 
issue. 
One of the specific objectives of this protocol is to assess the toxicity of the treatment. 
Due to the large number of variables within this protocol, i.e., ABM transplantation and 
Taxol administration, it is likely that any toxicity resulting from the gene transfer portion 
of the protocol will be missed. 
Dr. Krogstad said that there is concern about the possibility that malignant cells in the 
patient's bone marrow might be inadvertently transduced with the MDR gene in addition 
to the normal cells. Published data in the scientific literature indicates that between 30 
and 50% of breast cancer patients have bone marrow involvement; however, the extent 
[74] 
Recombinant DNA Research, Volume 17 
