Recombinant DNA Advisory Committee - 6/9-10/94 
Dr. Deisseroth explained that patients entered on this study will have Stage III/IV breast 
cancer and failed initial therapy but have not received Taxol. Subjects will have negative 
bone scans and negative marrow involvement as demonstrated by microscopic and 
immunohistochemical methods. The immunohistochemical assays are sufficiently 
sensitive to detect one contaminating cancer cell in 1 x 10^ normal cells. The 
combination of patient eligibility criteria and assay sensitivity will ensure that the MDR-1 
chemoprotection gene will not inadvertently transduce tumor cells. Prior to the 
collection of peripheral blood cells, subjects will receive a dose of cyclophosphamide to 
reduce the number of circulating cancer cells. CD34(+) selection of peripheral blood 
cells will further preclude the possibility of contaminating cancer cells since the latter are 
CD34(-). The proposed strategy of this study is that introduction of the MDR-1 
chemoprotection gene into CD34( + ) peripheral blood cells will allow delivery of high 
dose Taxol post-ABMT to eradicate breast cancer cells. 
Dr. Deisseroth stated that the 10% transduction efficiency observed in CD34(+) 
peripheral blood cells is equivalent to the transduction efficiency of CD34(+) bone 
marrow cells. Responding to the question of possible cancer cell contamination, he 
responded that the immunohistochemical assay used to screen patients is sensitive 
enough to easily identify patients who have cancer cells circulating in their peripheral 
blood. The bone marrow will be assayed for contaminating cancer cells. Since bone 
marrow has a contamination rate 1,000 times higher than that of peripheral blood 
mononuclear cells, a negative assay demonstrated on bone marrow cells reduces the 
probability of peripheral blood contamination to less that 1 in 1 x 10® cells. CD34 
selection should further reduce this possibility to less than 1 in 1 x 10^ to 1 x 10^° cells. 
Since a maximum of 2 x 10^ cells will be transduced, the chance of transducing the 
MDR-1 gene into a single cancer cell is extremely small. Any possible risk to patients is 
insignificant compared to the potential for benefit. He expects that 20 patients entered 
on the study should yield 10 evaluable patients, i.e., participation through completion of 
the study. 
Dr. Deisseroth responded to questions regarding the Informed Consent document. 
Patients will be monitored for life. MD Anderson Cancer Center will provide free 
medical care to uninsured patients who are residents of Texas. For those patients who 
have insurance, financial counselling will be provided to ensure that there is sufficient 
insurance coverage before admission to the protocol. Research-related costs will not be 
charged to patients; these costs are provided by research grants. Dr. Chase expressed 
concern about contradictory statements in the Informed Consent document regarding 
disclosure of financial obligations. Dr. Deisseroth responded that the Informed Consent 
document will be revised to clarify this issue and submitted to the IRB. 
Dr. Holmes commented that the IRB has formed a subcommittee specifically to address 
the issue on providing mechanisms for payment of medical costs that are not considered 
as routine patient care. Dr. Chase applauded this effort by the MD Anderson IRB and 
said that letters should be sent to other IRBs to urge similar action. Dr. Wivel noted 
that such an action is beyond the purview of the RAC. 
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Recombinant DNA Research, Volume 19 
