Recombinant DNA Advisory Committee - 09/9-10/93 
human cells, Dr. Podack stated that data derived from human cell lines, in addition to 
HeLa, indicate episomal presence based on high level IL-2 production. The level of ED2 
expression is a more pertinent parameter for the present study. Dr. Miller agreed with 
Dr. Podack's statement. Dr. Miller said that the risk of episomal DNA inadvertently 
infecting other cells, even if the cells carrying the DNA have been lethally irradiated, is 
quite remote. 
Committee Motion 
A motion was made by Dr. Miller and seconded by Mr. Capron to approve the protocol 
contingent upon review and approval of data demonstrating that cells obtained from 
patients can be successfully transduced with the proposed vector and that these 
transduced cells secrete * 50 units of 13^2/ml/lO 6 cells/24 hours. The motion passed by 
a vote of 18 in favor, 0 opposed, and no abstentions. 
V. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE THERAPY PROTOCOL ENTITLED: RETROVIRAL MEDIATED TRANSFER 
OF THE HUMAN MULTI-DRUG RESISTANCE GENE (MDR-1) INTO 
HEMATOPOIETIC STEM CELLS DURING AUTOLOGOUS TRANSPLANTATION 
AFTER INTENSIVE CHEMOTHERAPY FOR BREAST CANCER/DR. 
O'SHAUGHNESSY 
1 1 
Review-Dr. Parkman 
I 
I 
Dr. Walters called on Dr. Parkman to present his primary review of the protocol 
resubmitted by Dr. Joyce A. O'Shaughnessy, NIH, Bethesda, Maryland. This protocol 
was deferred at the December 1992 RAC meeting until the investigators could return to 
the full RAC with the following: (1) data demonstrating that human CD34( + ) cells have 
been transduced in vitro with the vector that will be used in the clinical protocol; (2) a 
description of the assays that will be used to measure gene expression, and demonstrate 
how this expression will be monitored in bone marrow and tumor cells; and (3) a 
description of the endpoint for determining efficacy (evaluation criteria), i.e., comparison 
of gene amplification and the rate of white blood cell recovery following Taxol 
treatments one and three. 
Dr. Parkman stated that the transplantation procedure is part of a freestanding clinical 
protocol that deals with autologous transplantation for patients with responsive Stage IV 
breast cancer following chemotherapy with ifosfamide, carboplatin, and etoposide. 
Patients will be transplanted with a combination of bone marrow and peripheral blood 
stem cells and will receive subsequent Taxol administration. The gene transfer portion 
of the proposed study is the only aspect of the protocol that requires RAC review. 
CD34( + ) stem cells will be isolated from bone marrow and peripheral blood. If 
adequate numbers of these cells are obtained, a portion will be transduced in vitro with a 
retrovirus vector expressing the MDR-1 gene. Both transduced and untransduced 
CD34( + ) cells will be reinfused back into the patients. Patients demonstrating 
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