Recombinant DNA Advisory Committee - 06/7-8/93 
Mento speculated that the packaging cell line may have a block that prevents re-infection 
by amphotropic virus. Such a block could prevent RCR detection by other assays such 
as the S + L' amplification test. 
Regarding the issue of virus formulation, Dr. Mento explained that the excipient added 
to increase stability of retrovirus particles has previously been tested in humans. The 
excipient formulation is proprietary information and has not been submitted in this 
application. He stated that Viagene would submit the formulation on a confidential 
basis if necessary. Dr. Miller stated that the formulation of the excipient should not 
present a problem from the recombinant DNA aspect. Dr. Chase, however, was 
concerned approving a protocol in which information has been withheld. Dr. Parkman 
and Mr. Capron suggested that the formulation could be submitted to ORDA and 
reviewed by RAC members on a confidential basis. 
Responding to Dr. Straus' question about allowing patients on the placebo group to 
crossover to receive the retrovirus preparations at a later time, Dr. Mento stated that 
this decision was made based on the fact that the placebo group was originally intended 
to be a control for the active treatment group in the assessment of CTL responses and 
other parameters. Recent studies have shown that comparisons within one group at 
different time points are more meaningful than comparisons to a placebo group. In the 
current design, the placebo group is primarily for comparing the short-term adverse 
effects of vector administration. Patient crossover at a later time point will not affect the 
investigational results. 
Dr. Galpin responded to the question of excluding patients on AZT from participation in 
this study. Most of the patients in this study will have CD4( + ) cell counts over 500; 
therefore, the study can be conducted without the necessity for AZT administration. On 
the question of confidentiality, patient identity will be known only to the physicians, not 
Viagene. The physicians negotiating informed consent will not be the Pis of this study. 
In answering a question raised by Dr. Smith on the possibility of altering the HIV host 
range through the amphotropic envelope gene of the packaging cells, Dr. W. French 
Anderson, University of Southern California, said that such a scenario is highly unlikely. 
Recombination between the HIV gpl20 and murine gp70 is unlikely to occur. Any 
recombinant would likely be less toxic than gpl20 alone. If any of the HIV genome 
were packaged in the murine amphotropic envelope, it would be destroyed by the host 
complement system. Dr. Mento commented that the retrovirus backbone used in the 
vector does not contain the amphotropic env gene. The vector preparations should be 
safe if they are free of RCR. Dr. Miller agreed that this hypothetical risk is a highly 
speculative situation. Mr. G'dali Braverman from Act Up expressed his support of 
Viagene submitting this protocol for RAC review. It is an encouraging phenomenon that 
industry has voluntary established dialogue with the RAC and the public. In closing, Dr. 
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Recombinant DNA Research, Volume 17 
