DM6 parental or y-IFN transduced tumor cells were also tested as target cells using an HLA-A2 
restricted, melanoma specific cytotoxic T-cell line. These HLA Class I restricted effector cells 
showed 161 lytic units (35%) per 10^ cells of activity against the parental DM6 line and 270 lytic 
units of activity against the gene transduced tumor line, an increase of 67% (Table DC). The 
marginally increased T-cell recognition of DM6/y-IFN may be related to the enhanced expression 
of T-cell defined tumor associated antigens presented in the context of the increased Class I HLA 
proteins. Consistent with this is the dramatic upward shift in the inhibition curve of antibody 
W6/32 in blocking studies using parental or EFN gene transduced DM6 as target cells (Figure 16). 
In this study, the same quantity of W6/32 reduced the lysis if DM6 by 61% but reduced lysis of 
DM6/y-IFN by only 16%. The data indicate that the increased HLA Class I antigens on the gene 
transduced tumor cells are fully functional to present melanoma associated, T-cell defined tumor 
antigens required for T-cell recognition. 
3.4 CONCLUSIONS 
Data from animal tumor models showed that the tumorigenic phenotype was, at least in part, due to 
poor anti-tumor immunity. The available evidence strongly suggests that the lack of effective 
immunity is due to poor CTL induction and not the inability of a tumor cell to act as a target for 
CTL lysis. Our in vitro studies with human melanoma immune responses showed a similar effect, 
since y-IFN transduction substantially increased CTL proliferative responses but did not 
dramatically improve the ability of the tumor cell to act as a target (Table VIII). The parallel 
between in vivo murine studies and in vitro human studies suggests that CTL responses in 
melanoma patients may be dramatically stimulated clinically by the administration of y-IFN 
transduced autologous tumor cells and that such responses could effectively recognize and destroy 
melanoma cells. 
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Recombinant DNA Research, Volume 17 
