Recombinant DNA Advisory Committee - 06/7-8/93 
XII. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE THERAPY PROTOCOL ENTITLED: A PRELIMINARY STUDY TO 
EVALUATE THE SAFETY AND BIOLOGIC EFFECTS OF MURINE RETROVIRAL 
VECTOR ENCODING HIV-I GENES [HIV-IT(V)] IN ASYMPTOMATIC SUBJECTS 
INFECTED WITH HIV-1 /DRS. GALPIN AND CASCIATO 
Review-Dr. Hirano 
Dr. Walters called on Dr. Hirano to present her primary review of the protocol 
submitted by Drs. Jeffrey E. Galpin of the University of Southern California, Los 
Angeles, California, and Dennis A. Casciato of the University of California, Los Angeles, 
California (sponsored by Viagene, Inc., San Diego, California). The overall goal of this 
study is to evaluate the use of retrovirus vector-mediated gene transfer for the treatment 
of human immunodeficiency virus (HlV)-infected individuals. The N2 retrovirus vector 
carrying env /rev gene of HIV-1 will be administered to asymptomatic HIV infected 
individuals. The hypothesis is that the vector will express the HIV env protein within 
cells and induce an augmented CTL response. This augmented response may slow or 
reverse disease progression. The safety and biological effects of the vector have been 
assessed in mice and in nonhuman primates. These in vivo studies demonstrated the lack 
of any acute or chronic toxicity and induction of enhanced CTL and antibody responses. 
The specific objective of this protocol is to evaluate these parameters in human subjects. 
Intramuscular injections will be administered monthly for 3 months and patients will be 
followed for evidence of virus replication, HIV burden, and HIV- 1-specific CTL 
responses. This will be a dose-escalation study with increasing multiplicities of the 
vector. 
Review-Dr. Straus (presented by Dr. Hirano) 
In Dr. Straus' absence, Dr. Hirano summarized his primary review of the protocol. Most 
of the questions raised by Dr. Straus have been satisfactorily answered by the Pis. Dr. 
Straus asked about the advantage of using a retrovirus vector to express the HIV env 
gene instead of direct injection of recombinant env protein. The Pis responded that the 
env protein produced by the retrovirus vector will be processed within the cell to induce 
cellular immunity while direct injection of env protein will only induce a humoral 
immune response. Dr. Straus asked whether the CTL responses induced by the injected 
HIV strain would cross react with other strains of HIV virus. Dr. Straus questioned the 
exclusion of patients being treated by antiviral drugs since this protocol is not an efficacy 
study and since antiviral drugs should not alter CTL responses. He asked why the Pis 
propose crossing-over with the placebo recipients in this Phase I study. 
Dr. Hirano agreed with Dr. Straus' concerns about the exclusion of patients receiving 
antiviral drug therapy, particularly in reference to the statement that azidothymidine 
Recombinant DNA Research, Volume 17 
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