immune system before it becomes severely compromised by HIV- 1 
disease. 
4. 2.2. 2 Generally, a long, symptomless period follows the initial acute infection 
with HTV-1 Infected individuals could, therefore, benefit from an 
immunotherapy that stimulates both potent HTV-1 specific CD8 + CTL, 
neutralizing antibodies, or both. CD8 + CTL are extremely potent 
"killers" of virally infected cells 1 1. The Class I MHC restricted CD8 + 
CTL system is the arm of the immune system that is most specifically 
designed to combat viral infections 12. HrV-IT (V) is a promising agent 
for clinical trials as a treatment in HTV-1 infection because cells 
transduced with HTV-IT (V) have been shown to specifically induce the 
CTL immune response of mice and macaques at doses that lack 
appreciable toxic side effects^. Although not yet administered 
clinically, Viagene has data indicating that HTV-IT (V) treated 
autologous cells can stimulate a CD8 + human CTL response in vitro x 
(using PBMC obtained from HTV-1 seropositive patients). In addition, 
HTV-IT (V)- treated mice can also elicit CD8 + CTL that selectively 
destroy cells expressing HIV-1 proteins in vitro. HTV-IT (V) also elicits 
a concomitant antibody response in the murine system directed against 
the HTV-1 niB envelope protein. 
4.2.3 Description of HIV-IT (V) 
4.2.3. 1 HTV-IT (V) is an intramuscularly (TM) injected HTV-1 immuno- 
therapeutic based on retroviral vector-mediated gene transfer technology 
that provides for the delivery of the env gene segment of the HTV-1 nTR 
strain directly into patient cells. The retroviral vector containing the 
gene is subjected to Quality Control testing, and injected into multiple 
IM sites. Proteins expressed from this gene and presented on the 
surface of transduced recipient cells may cause significant stimulation of 
immune responses, and in particular, the CD8 + CTL response. An 
overview of the gene transfer procedure used to generate HIV-IT (V) is 
10 Robert-Guroff, M„ et al, Nature, 316:72-74 (1985). 
1 1 Klavinskis, L.S., et al, J. Virol., 63:431 1-4316 (1988). 
^Koenig, S., et al, J. Immunol., 145:127-135 (1990). 
'-^Warner J.F. et al, AIDS Res. & Human Retroviruses, 7:645-655, (1991) 
Recombinant DNA Research, Volume 17 
