Recombinant DNA Advisory Committee - 2/10-11/92 
population will differentiate into lymphocytes and express the gene product. 
Dr. Leventhal stated that she could not vote on this protocol amendment until the RAC 
receives the following: (1) a formal outline describing the studies to be performed on 
patients' CD34( + ) cells that will demonstrate transduction and ADA expression in these 
cells; (2) a formal outline describing the studies to be conducted that will demonstrate the 
efficacy of the CD34( + ) ADA transduced cells in terms of reconstituting immune function 
and particularly vis-a-vis the T lymphocytes that have been ADA-reconstituted; and (3) a 
formal outline of the toxicity criteria that would be used for stopping G-CSF. Conditional 
approval should be based on receiving these three items. 
Dr. Carmen accepted Dr. Leventhal's amendment as a friendly amendment. Mr. Mannix 
moved to table Dr. Carmen's motion to approve the protocol for 25 hours allowing time 
for the investigators to respond to Dr. Leventhal's request for the written outlines. Mr. 
Barton seconded the motion. Dr. B. Murray asked if there were any objections to tabling 
the motion. As there were no objections, the motion to table the discussion for 25 hours 
was passed by a vote of 13 in favor, 0 opposed, and no abstentions. 
V. PROPOSED ADDITION TO APPENDIX D OF THE NIH GUIDELINES 
REGARDING A HUMAN GENE THERAPY PROTOCOL ENTITLED: GENE 
TRANSFER FOR THE TREATMENT OF CANCER 
Review-Dr. Gellert 
Dr. Gellert summarized the protocol as a proposed treatment for ovarian cancer. Patients 
would be infused with cells from a human ovarian cancer cell line that has been 
transduced with the thymidine kinase (TK) gene derived from herpes virus (HSV-TK). 
These TK( + ) cells can be selectively killed with ganciclovir. The investigators propose 
that injection of these transduced cells could possibly stimulate an immune response that 
would effect killing of the primary tumor. There were three problematic issues: (1) the 
appropriateness of the animal model; (2) the possible use of apoptotic vesicles; and (3) the 
mechanism by which this therapy is supposed to be successful. 
Addressing the issue of the appropriateness of the animal model, Dr. Gellert stated the 
revised protocol calls for injecting the primary tumor cells six days prior to treatment. The 
investigators observed a slight prolonging of survival following TK( + ) cell administration; 
however, the effect was less than when the primary tumor was injected just prior to 
treatment. This result raised the question of how this treatment will translate to humans. 
Both the treated and untreated mice eventually died of their tumors. 
Dr. Gellert cited an experiment that demonstrates that apoptotic vesicles kill cells in vitro. 
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