in combination with adoptive transfer or TIL therapy. These 
studies will provide an alternative strategy for the 
immunotherapy of malignancy and allow definition of the mechanism 
of immune rejection of tumor cells. Adaptations of this method 
may also eventually be applied to the treatment of other human 
diseases . 
1.3 Direct gene transfer in vivo. 
The conventional approach to immunotherapy is based on the 
modification of T lymphocytes or tumor cells in vitro . followed 
by reintroduction in vivo . Limitations of this approach include 
1) the need to establish a cell line from each experimental 
subject and to avoid allogeneic tissue rejection, 2) concerns 
about alteration of the phenotype of cells propagated in tissue 
culture, 3) the outgrowth of aberrant transformed cells, and 4) 
the time and effort required to establish cell lines, introduce 
genes, select for a relevant phenotype and characterize the cells 
prior to reintroduction into animals. 
We have therefore developed an alternative approach in which 
recombinant genes are introduced directly into cells in vivo . 
Introduction of recombinant genes into cells in vivo provides a 
powerful method to study their effects in a relevant setting in 
humans. This approach has been utilized by our laboratory to 
study the effect of recombinant gene expression within transduced 
vascular cells in a localized arterial segment in several animal 
models. We have used two delivery vehicles, retroviral vectors 
and DNA/ liposome-mediated transfection. Of these two approaches, 
the DNA/liposome method can be more readily adapted to the 
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