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 IIIBenv) encoding the HIV-1 IIIB envelope (env) protein. Preclinical studies have 
demonstrated the ability of the N2 IIIBenv vector to induce immune responses in mice, 
Rhesus monkeys, and baboons. Specifically, the N2 IIIBenv vector was capable of inducing 
HIV-1 IIIBenv-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 placebo-controlled clinical trial involves the direct administration of the N2 
IIIBenv retroviral vector or diluent control to HIV-infected, seropositive, asymptomatic 
individuals not currently receiving anti-retroviral treatment. The direct vector treatment 
consists of a series of three monthly intramuscular injections of the test article using a 
two-tier dosing schedule. 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 normal 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 
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