Recombinant DNA Advisory Committee - 03/1-2/93 
In response to Dr. Carmen's question about the status of the immunodeficient mouse 
model, Dr. Bank explained that CD34( + ) cells have been transferred to severe combined 
immunodeficient (SCID) mice; however, this procedure is difficult and the results are 
inconsistent. 
With regard to Taxol administration, Dr. Bank explained that numerous breast cancer 
patients have received Taxol administration at Columbia University; however, they have 
not received bone marrow transplants. Dr. Parkman stated that the addition of ABM 
presents a very different biological setting than Taxol administration alone. Data must 
be submitted from patients that have received both Taxol and ABM transplantation. 
This data does not necessarily have to be derived from breast cancer patients. Data 
from 3 patients does not provide sufficient justification for this protocol. 
Other Comments 
Dr. Parkman explained that in order to draw a conclusion about the protective effect of 
the proposed therapy, there must be criteria established for defining a response to Taxol 
administration alone. Taxol response must be considered in addition to gene 
transduction and expression. Dr. Hesdorffer responded that patients will continue to be 
accrued onto Taxol protocols who have had ABM transplantation without transduction. 
Of the 3 patients who received ABM transplantation and Taxol administration, 1 ovarian 
cancer and 1 breast cancer patient demonstrated a response. Data is still being accrued 
on the third patient. Dr. Parkman explained that in order for the RAC to approve this 
protocol, the risk to the patient must be assessable. Since the response to Taxol 
administration and untransduced ABM cells alone is unknown, the effect of the inserted 
MDR gene cannot be evaluated. 
Dr. Leventhal stated that the investigators are obligated to define a stopping rule based 
on their clinical experience if adverse effects occur, i.e., aplasia, resulting from this 
treatment. Dr. Bank responded that they have defined toxicity criteria for giving patients 
recurrent doses of Taxol after ABM transplantation, and that Taxol will not be 
administered to patients until their white counts have reached 300-500. 
Dr. Bank responded to Dr. Krogstad's question about distinguishing between gene 
expression resulting from the transduced gene and natural expression of MDR from 
genomic DNA. The inserted MDR gene can be distinguished from naturai MDR by the 
following: (1) there is a single mutation that is distinguishable by reverse PCR, (2) 
glycine is substituted for a valine at position 185, and (3) there are different sequences in 
the 5' end. 
With regard to the assessment of toxicity, Dr. Bank responded that if any patien* 
develops a lymphoma or other type of tumor, the investigators will look for i/' r _iticnal 
i 
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Recombinant DNA Research, Volume 17 
