gene transfer protocols have been designed to monitor the traffic 
of lymphocytes into melanoma tumors (17) or to introduce cytokine 
genes into tumor cells to stimulate the host's immune response to 
residual tumor (18) . 
We have recently developed a novel molecular genetic 
intervention for human malignancy. This approach relies on the 
direct transmission of recombinant genes into established tumors 
in vivo to genetically modify them as they grow in situ. In 
animal models , introduction of a gene encoding a foreign major 
histocompatibility (MHC) protein (class I) in vivo signals the 
immune system to respond to the foreign antigen (5,19). More 
importantly, when this gene is transduced into established tumors 
in vivo, a cytolytic T cell response is also generated against 
unmodified tumor cells. In murine models, this approach has led 
to significant reductions in tumor growth and, in some cases, 
complete remission (5) . Based on these studies, we received 
approval from the Recombinant DNA Advisory Committee of the 
National Institutes of Health to conduct a human clinical 
protocol using direct transfer of a human transplantation antigen 
gene in an effort to treat malignancy. This protocol proposed to 
perform direct gene transfer in humans and to utilize a non-viral 
vector which reduces several safety concerns about viral vectors. 
This clinical trial involved the treatment of patients with 
metastatic melanoma at subcutaneous lesions. The treatment 
consists of intratumoral injection of the human class I MHC gene, 
HLA-B7 complex, to a cationic liposome, DC-Cholesterol (2,20). 
These patients received escalating doses of the DNA liposome 
Recombinant DNA Research, Volume 17 
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