Galpin/DA/N2 IIIBenv 
presentation pathway. Because retroviral vectors are non-replicating and non-cytopathic to 
cells, one would predict negligible perturbation of normal cellular processes following 
retroviral vector transduction. Therefore, retroviral vector-mediated gene transfer may 
provide advantages for antigen presentation compared to that of replicating vector systems, 
or the natural viral infection. HIV-IT (V) is capable of delivering the genes that encode the 
HIV-1 env/rev proteins. These proteins appear in the cytoplasm of HIV-IT (V) transduced 
cells as endogenous proteins, capable of entering the endogenous antigen presentation 
pathway necessary for CD8 + CTL induction. Moreover, HIV-IT (V)-delivered env gene 
product is also expressed on the cell surface and can enter the exogenous pathway, thus 
activating antibody responses. The preclinical studies described here demonstrate the ability 
of non-replicating murine retroviral vectors to induce HIV-specific humoral and cellular 
immune responses, particularly CTL responses, in murine and non-human primate models. 
The potential benefits of using HIV-IT(V) to induce HIV-specific immune responses in 
HIV-infected patients are: 
• HIV antigens produced intracellularly should be processed and presented to the 
immune system in the context of MHC-I, 
• HIV antigens should be presented by treated cells in the absence of potentially 
perturbing HIV infection processes, and 
• augmented HIV-specific CTL and antibody responses should be induced. 
The current treatment for HIV infection involves the use of reverse transcriptase (RT) 
inhibitors, e.g., AZT, ddl, DDC, or D4T as single or combination therapy to slow viral 
replication. Triple therapy using unique RT inhibitors along with either immune modulators 
or selectively different HIV-1 inhibitors also demonstrates promise. These therapies show 
partial clinical efficacy over relatively short periods of time, but do not appear to effectively 
halt disease progression. In addition, elimination of previously infected cells is not proven to 
occur with these interventions. Moreover, HIV is capable of drug resistant 
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Recombinant DNA Research, Volume 17 
