Galpin/DA/N2 IIIBenv 
1.0 OBJECTIVES AND RATIONALE OF THE RESEARCH 
The objective of this clinical study is to evaluate the use of retroviral vector-mediated 
gene transfer for the treatment of human immunodeficiency virus (HlV)-infected individuals. 
This clinical study will use a genetically engineered, non-replicating murine retroviral vector 
encoding the HIV-1 IIIB envelope (env) and rev proteins, termed the HIV 
immunotherapeutic vector [HIV-IT(V)]; and will evaluate the acute toxicity and potential 
enhancement of immune responses in humans following the direct administration of HIV- 
IT(V). The intended patient population for this study will be HIV-seropositive, 
asymptomatic subjects not currently receiving anti-retroviral therapy. It is believed that this 
patient population will provide relevant safety and immunological data needed to evaluate 
the use of HIV-IT(V). 
The role of immune responses in controlling the disease process of human 
immunodeficiency virus (HIV) infection is poorly understood. HIV-infected patients exhibit 
both humoral 1 ^, 3,4 anc j cellular 5 immune reactivities, and yet continue to show disease 
progression. Cytotoxic T lymphocyte (CTL) responses mediated by CD8 + , Class I major 
histocompatibility complex (MHC)-restricted T cells have been demonstrated in animal 
models to be a major anti-viral defense mechanism impacting disease severity and 
duration 6 - 7 ’ 8 . CTL capable of lysing target cells expressing HIV-1 proteins have been 
detected in HIV-1 infected patients 9 - 10 ’ 11 ’^, 13, 14, 15 anc j ma y contribute to controlling the early 
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5 Popovic, M., et al., J. Virol., 224:497-500 (1984). 
6 Rouse, R.T., et al., Rev. Infect Dis., 10:19-33 (1988). 
7 Kast, W.M., et al., J. Exp. Med., 164:723-738 (1986). 
8 KJavinskis, L.S., et al.,./. Virol., 63:431 1-4316 (1989). 
9 Walker, B.D., et al.. Nature, 328:345-348 (1987). 
10 Plata, F.B., et al.. Nature, 328:348-351 (1987). 
1 ^ixon, D.F., et al., Nature, 336:484487 (1988). 
^Walker, B.D., et al.. Science, 240:64-66 (1988). 
13 Koenig, S„ et al., Proc. Natl. Acad. Sci. (USA). 85:8638-8642 (1988). 
' 4 Chenciner, N., et al., Eur. J. Immunol., 19:1537-1544 (1989). 
15 Koenig, S„ et al.,7. Immunol., 145:127-135 (1990). 
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