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 p-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 additional clinical sites, 
the Mayo Clinic, the Arizona Cancer Center, and the University of Chicago Medical Center. 
These studies will facilitate the development of other approaches, using different recombinant 
genes or in combination with cytokines or adoptive T-ceU therapy, to augment tumor 
immunity, and allow for greater potential efficacy. This method will also establish the safety of 
this non-viral approach to gene therapy, which could potentially be extended to treat a variety 
of other human diseases. 
Recombinant DNA Research, Volume 19 
[203] 
