Scientific Abstract 
Scientific Abstract 
The goal of immunotherapy is to stimulate the immune system by modification 
of tumor cells or expansion of lymphocytes which respond specifically to tumor 
antigens. In this study, we will apply techniques of direct gene transfer to enhance 
immune response against tumors in vivo. Patients with advanced cancer who have 
failed all effective therapy will be treated by injection of a DNA/lipid complex directly 
within the tumor. DNA will be used which encodes a heterodimeric cell surface 
protein recognized in the transplantation response. These genes include the HLA-B7 
histocompatibility antigen and (3-2 microglobulin gene in a non-viral plasmid 
eukaryotic expression vector. For this vector, a safe and effective dose to introduce this 
recombinant gene in HLA-B7 negative patients will be established. HLA-B7 expression 
will be confirmed in vivo, and the immune response stimulated by the expression of 
this antigen will be characterized. We will also determine whether this treatment 
facilitates tumor regression. This study employs the same study drug as Dr. Gary 
Nabel of the University of Michigan, previously proposed gene therapy protocol, but 
expands the study to two other clinical sites, the Mayo Clinic and the Arizona Cancer 
Center. These studies will facilitate the development of other approaches, using 
different recombinant genes or in combination with cytokines or adoptive T-cell 
therapy, to augment tumor immunity, and allow for greater potential efficacy. This 
method will also establish the safety on this non-viral approach to gene therapy, which 
could potentially be extended to treat a variety of other human diseases. 
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Recombinant DNA Research, Volume 18 
