In summary of the safety data, there have been no side effects or toxic 
reactions due to the gene transfer. In addition, there has been no evidence 
of replication-competent virus in any retroviral supernatant used for clinical 
studies, no consistent differences in the pattern of cell growth, phenotype, 
or cytotoxic function in any preparation of gene-transduced TIL, and no 
lymphocyte population has developed IL-2 independence. There has also 
been no evidence of viral exposure for any of the 10 patients based on 
Western analysis as well as 3T3 amplification with S-i-L- cell assay of 
patient serum. In short, the data acquired to date demonstrate no 
abnormalities, side effects, toxicity's, or pathology due to the retroviral- 
mediated gene transfer procedure. 
2.3 Rationale for the Current Study 
The proposed protocol is designed to evaluate the safety and potential value of 
genetically modifying T lymphocytes in an attempt to prevent or control HIV infection. 
A large amount of experimental data have accumulated which suggest that the CD8-t- T 
cell response may represent the major and earliest immune response to HIV infection. 
For example, studies have shown that anti-HIV CTL are present in the PBMC of HIV 
sero-negative individuals exposed to HIV (36). Although a high frequency of HIV 
antigen-specific CD8-I- T cells are also found in the peripheral blood of asymptomatic 
HIV seropositive patients, a selective decline in HIV specific CTLs is observed in 
patients as they progress to later stages of the disease, even though polyclonal cytolytic 
activity in these patients appears to be unaffected (37). This suggests that a breakdown 
of the host cell-mediated immune response is associated with progression to AIDS. In 
vitro studies have not only shown that anti-HIV CD8+ cells exhibit cytolytic activity 
toward HIV infected targets, but also have demonstrated that these cells have the ability 
to inhibit HIV replication in lymphocyte cultures (38). These results suggest that 
adoptive transfer of HIV specific CTLs may have potential as immunotherapy for HIV 
infected individuals. In order to generate large numbers of anti-HIV specific CTL’s 
suitable for infusion into AIDS patients with various HLA types, a method has been 
developed using retroviral mediated gene transfer to insert a HIV-targeting gene into 
primary CD8-I- T cells. The genetically marked cells are then purified and expanded, 
and therefore large numbers of HIV specific CTL’s can be generated for infusion. 
From rodent adoptive immunotherapy studies, it has been determined that anti-viral 
effects can be demonstrated; however, large numbers of specific anti-viral CTL’s need 
to be infused. 
This study will provide data on the effect of infusion of specific anti-HIV cytotoxic 
CD8+ T cells into HIV infected individuals. In addition, the present study will permit 
the elucidation of effects of infusion of specific anti-HIV effector cells as opposed to 
infusion of bulk populations of polyclonal CD8+ T cells. By monitoring functional 
immune status, viral burden, and end organ function, we hope to determine whether 
this potential therapeutic approach is feasible and safe. This study will form the | 
baseline to which other protocols using lymphocytes directly from HIV patients will be ( 
compared. > 
3. EXPERIMENTAL PLAN 
3.1 Study Design 
• Phase I / II 
• Patient Population - HIV-infected patients with an uninfected syngeneic twin 
• Randomized 
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