Recombinant DMA Advisory Committee - 6/9-10/94 
Acute Hepatic Faflurc 
0 
1 
1 
Familial Hypcicfaolestcrolcmia 
1 
0 
1 
Gaucher Disease 
3 
0 
3 
Booe Marrow Marking/ Cancer 
0 
15 
15 
HTV(+) 
5 
2 
7 
Alpha-1-Antitiypsin Dcfideocy/Acute Lung 
Injury 
1 
0 
1 
IX. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE TRANSFER PROTOCOL ENTITLED: USE OF SAFETY-MODIFIED 
RETROVIRUSES TO INTRODUCE CHEMOTHERAPY RESISTANCE SEQUENCES 
INTO NORMAL HEMATOPOIETIC CELLS FOR CHEMOPROTECTION DURING 
THE THERAPY OF BREAST CANCER: A PILOT TRL4L/DRS. DEISSEROTH, 
HORTOBAGYI, CHAMPLIN, AND HOLMES 
Review— Dr. Brinckerhoff (presented by Dr. Dronamr^u) 
Dr. Walters called on Dr. Dronamraju to present the primary written review of Dr. 
Brinckerhoff for the protocol submitted by Drs. Albert Deisseroth, Gabriel Hortobagyi, 
Richard Champlin, and Frankie Holmes of MD Anderson Cancer Center, Houston, 
Texas. Dr. Brinckerhoff stated that this study is based on Protocol #9306-044, previously 
approved by the RAC for the treatment of ovarian cancer. This proposal differs in three 
aspects: (1) patient eligibility is limited to breast cancer not ovarian cancer; (2) 
peripheral blood mononuclear cells will be transduced with the gene for multidrug 
resistance type-1 (MDR-1), not autologous bone marrow cells; and (3) the peripheral 
blood cells will undergo immunohistochemical analysis to rule out the presence of 
contaminating breast cancer cells. 
A retrovirus vector encoding the MDR-1 gene will be used to transduce autologous 
peripheral blood hematopoietic stem cells. Prior to transduction, these stem cells will be 
cryopreserved while the patient undergoes chemotherapy. Following chemotherapy, 50% 
of the CD34(-f-) cells will be thawed, transduced with the MDR-1 vector, and infused 
into the patient. The MDR-1 marked cells will be monitored by means of a 
methylcellulose late progenitor colony culture system and a PCR assay for the MDR-1 
gene. The acquisition of chemotherapy resistance by stem cells will be monitored using 
culture assays by drug selection. These studies will evaluate whether the introduction of 
the MDR-1 gene into peripheral blood CD34( + ) cells confers chemotherapy resistance; 
therefore, allowing for a more intensive Taxol regimen. Ultimately, increased doses of 
chemotherapeutic agents may lead to improved prognosis for breast cancer patients. 
Dr. Brinckerhoff stated that this proposal is a logical extension of Dr. Deisseroth's 
ongoing ovarian cancer protocol (Protocol #9306-044). Although this protocol may have 
qualified for the Minor Modification process, a change in the tumor target raises a 
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Recombinant DNA Research, Volume 19 
