Human Gene Therapy Subcommittee - 11/21-22/91 
that transformation assays will be performed with the original vector. Dr. Walters asked 
if the assays to determine efficacy of the new vector will be completed prior to the 
February 1992 RAC meeting? Dr. Nabel said that these experiment will probably be 
completed prior to the next RAC meeting. 
Dr. Wivel restated the stipulations for approval of Dr. Nabel's protocol: (1) changes to 
the consent form regarding inclusion/exclusion criteria, (2) expansion of the clinical 
protocol regarding biopsy schedules, (3) review of the vector structure to the satisfaction 
of the reviewers, and (4) submission of data regarding the integration status into the 
tumor. The motion passed by a vote of 13 in favor, 0 opposed, and no abstentions. 
PROPOSED AMENDMENT TO APPENDIX D OF THE NIH GUIDELINES 
REGARDING HUMAN GENE TRANSFER PROTOCOL ENTITLED 
RETROVIRAL-MEDIA TED GENE TRANSFER OF BONE MARROW CELLS 
DURING AUTOLOGOUS BONE MARROW TRANSPLANTATION FOR ACUTE 
LEUKEMIA /Dr. Cometta: 
Review-Dr. Gellert 
Dr. Walters called on Dr. Gellert to present his primary review of the protocol submitted 
by Dr. Kenneth Cometta of Indiana University, Indianapolis, Indiana. Dr. Gellert stated 
that this protocol is a resubmission of a protocol that was reviewed and deferred at the 
November 30, 1990, HGTS meeting. This deferral was based on the need for additional 
preclinical data. The objective of the revised protocol is to determine if relapse in 
leukemia patients results from the tumor burden that remains in the patient or from 
tumor cells that are reinfused at the time of bone marrow transplant. During the 
original review of this protocol, the HGTS expressed concern that Dr. Cometta could 
not mark cells efficiently enough to allow detection. At that time, transduction efficiency 
data had been obtained from only one patient, indicating that marking occurred at a 1% 
frequency. The investigators have currently submitted marking data on 5 patients. Data 
derived from 2 of these 5 patients demonstrate a transduction frequency between 4 and 
5%. Data are not available from the remaining 3 patients because of technical 
difficulties resulting from the inability of cells to grow in methylcellulose. Dr. Gellert 
explained that the HGTS had deferred approval of this protocol until quantitative 
transduction efficiency data were obtained in 6 patients; Dr. Cometta has provided 
quantitative data on only 2 patients. Therefore, there is not any overwhelming 
confidence that the experiment will actually work. 
Dr. Gellert described new animal data in which mice were transplanted with 10 6 LNL6 
marked lymphoma cells; integration occurred in approximately 3,000 sites. A restriction 
digest resulted in a total DNA smear. Conversely, when these transduced cells were 
reisolated from these animals, only a few clones grew. There is a selection for growth in 
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