Scientific Abstract 
SCIENTIFIC ABSTRACT OF THE STUDY 
This gene therapy protocol involves the use of retroviral vector-mediated gene transfer as treatment for 
human immunodeficiency virus (HlV)-infected individuals. The protocol employs a genetically engineered, 
non-replicating, amphotropic murine retroviral vector (N2 MBenv) encoding the HIV-1 IIIB envelope (ENV 
and REV) proteins. Preclinical studies have demonstrated the ability of the N2 IIIBenv/rev vector to induce 
immune responses in mice, Rhesus monkeys, and baboons. Specifically, the N2 IIIBenv/rev vector was 
capable of inducing HIV-1 MBenv/rev-specific CD8+ cytotoxic T lymphocyte (CTL) and antibody responses 
in these animals. Murine CTL induced by vector transduced cells also exhibited crossreactivity by lysing cells 
infected with different HIV-1 prototypic strains and clinical isolates. A balanced in vivo immune attack by 
HIV-specific CTL and antibody responses would be expected to eliminate HIV-infected cells and clear cell- 
free virus, respectively, from an infected individual. 
The Phase I/n clinical trial involves the direct administration of the N2 IIIBenv/rev retroviral vector to 
HIV-infected, seropositive, asymptomatic individuals. The direct vector treatment consists of a series of three 
monthly intramuscular injections of the test article. The packaging cell line, producer cell line, and processed 
vector material have undergone extensive quality control analysis for the presence of contaminating agents. 
Treated individuals will be evaluated for acute toxicity and for routine clinical parameters, CD4 levels, HIV- 
specific CTL responses, and viral load prior to, during, and following treatment. The treated subjects will 
also be requested to participate in follow-up for at least three years to identify long-term treatment effects and 
to evaluate their disease progression. 
The study protocol is designed to initially evaluate the safety of the direct administration of retroviral 
vector-mediated gene therapy as a treatment for individuals with a life-threatening disease. However, 
functional, biological and clinical disease parameters will be monitored as well to provide a basis for additional 
human studies. 
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Recombinant DNA Research, Volume 18 
