Recombinant DNA Advisory Committee - 6/9-10/94 
Dr. Deisseroth said that no patients have been entered on the ovarian cancer protocol 
because FDA approval is pending. 
Dr. Richard Cote of the University of Southern California (co-investigator) explained the 
immunohistochemical assay to detect contaminating cancer cells in peripheral blood and 
bone marrow samples. The test employs a mixture of monoclonal antibodies directed to 
cell surface glycoproteins and cytoskeletal elements of cells of epithelial origin including 
breast and ovarian carcinoma cells. He described spiking experiments involving a 
mixture of breast cancer and normal bone marrow or peripheral blood CD34(+) cells. 
At varying concentrations, between 2 and 5 tumor cells were detectable among 1 x 10*^ 
normal cells. The presence of breast cancer cells in bone marrow is biologically relevant 
since patients are more likely to have recurrence at this site following chemotherapy. 
Dr. Deisseroth reiterated that screening patients for bone marrow metastases is a major 
safety feature. 
Dr. Deisseroth described murine experiments in which CD34( + ) cells were transduced 
with MDR-1. These mice were resistant to Taxol at a maximum dose of 30 mg/kg body 
weight. This dose is equivalent to the highest dose proposed for the human study; 
therefore, the same degree of safety is expected for the human protocol. In response to 
Ms. Meyers' written comments. Dr. Deisseroth said that patients will undergo life-long 
follow-up. There is no manufacturer involved in the vector production; the vectors will 
be produced in the investigators' laboratory. 
Dr. Anderson commented on his personal experience regarding negotiation of medical 
coverage with the local IRB. IRB negotiation involves the IRB as well as the hospital 
administrators, board of trustees, and legal counsel. Ms. Buc responded that extensive 
negotiation is required only for deciding who is responsible for such costs. The issue of 
Informed Consent document clarification merely involves an amendment. Such 
amendments are easily dealt with at the IRB level. Dr. Deisseroth noted that most 
patients entered on this study have failed numerous other treatments. The "spirit" of the 
Informed Consent document is disclosure, i.e., possible unforeseen complications not 
directly related to gene therapy. Medical care will be provided to subjects independent 
of their economic status. 
Committee Motion 
The RAC approved a motion made by Dr. Dronamraju and seconded by Dr. Parkman to 
accept the protocol submitted by Drs. Albert Deisseroth, Gabriel Hortobagyi, Richard 
Champlin, and Frankie Holmes of MD Anderson Cancer Center, Houston, Texas, by a 
vote of 13 in favor, 0 opposed, and no abstentions. 
X. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE TRANSFER PROTOCOL ENTITLED: RETROVIRAL MEDIATED GENE 
TRANSFER OF THE FANCONI ANEMIA COMPLEMENTATION GROUP C GENE 
TO HEMATOPOIETIC PROGENITORS OF GROUP C PATIENTS /DRS, LIU AND 
YOUNG 
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