Recombinant DNA Advisory Committee - 06/7-8/93 
(AZT) (an antiviral drug) increases CTL responses in HIV patients. Dr. Hirano noted 
that the Pis have stated that all safety testing on the vector/producer cell line are 
satisfactory. This statement is meaningless unless one knows the specific fractions of the 
production lot that were tested and how these aliquots correlate with the proposed 
patient doses. Safety testing in terms of patient-dose equivalents would be a more 
meaningful approach. She questioned whether the phenotypes of CD8( + ) and CD4( + ) 
CTL responses differ between mice and humans. 
Review-Dr. Zallen 
Dr. Zallen raised specific concerns regarding the proposed protocol. Why is patient 
selection restricted to those individuals who have no early signs of acquired 
immunodeficiency syndrome (AIDS) and who have a CD4( + ) count above 400? In their 
written responses, Pis responded that this protocol is a Phase I study in which patients 
are targeted in an effort to minimize any possible masking of product-attributable 
toxicities due to the onset of progressive disease. The Informed Consent document is 
very well written, and she suggested several minor changes such as using the term "gene 
transfer" instead of "gene therapy." There may be a possible conflict of interest in the 
informed consent process; namely, since the Pis are the primary care physicians, they are 
not the most appropriate persons to act as negotiators for obtaining informed consent. 
She noted that the Pis included limited research credentials in their submission. What is 
the function of the Monitoring Board? How does the Monitoring Board affect Pis' 
decision-making? How will patient confidentiality be assured? 
Other Comments 
Dr. Smith proposed a hypothetical event in which an HIV virus with an altered host 
range could result from the retrovirus transfection protocol used in these patients. 
Theoretically, such an event could occur if an amphotropic env gene from the packaging 
cells is transduced by the retrovirus vector into the HIV-producing cells of the patients. 
An altered host range of HIV then could arise either through a recombination event 
between HIV and the amphotropic env gene or through transient production of a 
pseudotype virus of HIV with the amphotropic envelope. A pseudotyped HIV could 
result in uncertain toxicity in the patient or others. Dr. Smith inquired whether this 
hypothetical scenario could pose a problem in this study. Dr. Geiduschek suggested that 
the use of another unrelated vector, such as a DNA virus, could circumvent such a 
scenario. 
Dr. Parkman noted that there is a threshold virus dose in eliciting CTL responses in 
animal experiments. The dose proposed for this human study is below the threshold for 
CTL responses in animal models. Ms. Meyers commented that the Informed Consent 
document is well written and suggested that a statement should be included about a 
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Recombinant DNA Research, Volume 17 
