I 
j as well as previously unrecognized antigens in unmodified tumor 
V 
[ cells. The introduction of an allogeneic MHC gene directly into 
I 
tumors in vivo has induced partial tumor regressions, as well as 
( 
the specific cytotoxic T cell response to other antigens 
described above. In murine systems, we continue to optimize this 
gene delivery approach and characterize the cellular basis of 
this protective response, relevant cytokines which mediate this 
effect, and the nature of tumor specific antigens recognized by 
activated cytolytic T cells. This approach is also being used to 
introduce other recombinant genes with anti-tumor effects, such 
as tumor necrosis factor-a, into tumors. 
Because this approach employs direct gene transfer in vivo . 
it can be applied easily in a clinical setting to spontaneously 
arising tumors, alone or in combination with cytokines or other 
adjuvant treatments, including TIL cells, to augment tumor 
immunity. In this study, we propose a phase I clinical trial to 
evaluate the safety and appropriate dosage to introduce a 
recombinant HLA-B7 antigen into human tumors in vivo . 
Recombinant gene expression in vivo will be documented, and the 
specificity and mechanism of the immune response will be 
characterized. Escalating treatment regimens will be used and 
tumor growth evaluated. These studies will define the safety of 
this approach to the immunotherapy of malignancy and may provide 
therapeutic effects for patients. Adaptations of this approach 
might also prove useful in the treatment of other human diseases. 
Recombinant DNA Research, Volume 15 
[403] 
