(P18MB) derived from the V3 region of the HTV-Itttr envelope 
protein. The HIV-IT (V)-induced CTL also lyse target cells coated with 
the P18MN peptide derived from the equivalent V3 region of the HTV- 
1MN envelope protein. Similar CTL crossreactivity directed against 
proteins of different HIV-1 isolates has been demonstrated following 
immunization of mice with the syngeneic cells transduced with HIV-IT 
(V). Thus, the CTL response appears to exhibit broad reactivity or 
clinical coverage against diverse HIV-1 strains. Mice treated with HTV- 
IT (V) have also produced antibodies that specifically react to the HIV- 
l TTTR envelope protein. Mice were immunized by intramuscular 
injections several times and their serum tested for reactivity (binding) to 
gpl20 (Figure 4). 
4. 2.4. 5 Rhesus macaques have been immunized with HIV-IT (V), resulting in 
the production of HTV- 1 specific CTL. The intramuscular 
administration of successive doses of HIV-IT (V) to Rhesus macaques 
has resulted in the development of HTV-1 ENV specific CTL responses. 
Data from a treated macaque are shown in Figure 5. 
4. 2. 4. 6 Blood from HIV-1 infected patients has been examined to see whether 
anti-HTV-1 specific CTL responses could be amplified using HTV-IT 
(V) treated autologous cells. Figure 6 shows that PBMC from an HTV- 
1 infected individual can be reliably restimulated by HTV-IT (V) 
transduced autologous cells in order to expand the number and potency 
of anti-HIV- 1 ENV specific CD8 + CTL in vitro. Restimulated CTL 
from the patient lyse autologous cells expressing HIV-lmB env. 
However, the restimulated cells do not lyse non-transduced patient cells 
(control). These data support the view that human CD8 + CTL exist in 
H3V-1 infected individuals and can be stimulated to increased activation 
by HIV-IT transduced autologous cells. It will be important to ascertain 
whether a similar triggering phenomenon can occur in vivo. 
4. 2. 4. 7 In summary, preclinical data support the view that HIV-IT (V) can be 
safely administered to both mice and non-human primates, that strong 
CD8 + CTL and antibody responses can be induced in animal models, 
that cross-reactive immune responses between divergent HIV strains 
have been demonstrated by HTV-IT (V) induced murine CTL, and that 
HIV-IT (V) transduced cells can amplify in vitro, pre-existing CD8 ’ 
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Recombinant DNA Research, Volume 17 
