CLINICAL PROTOCOL 
Product: VCL-1102 
July 7, 1994 
VICAL INC. 
9373 Towne Centre Dr., Ste. 100 
San Diego, CA 92121 
direct gene transfer with a retroviral vector or DNA lipid complex (39). 
With either delivery system, expression of the recombinant HLA-B7 gene 
product could be demonstrated at specific sites within the vessel wall. 
More importantly, the expression of this foreign histocompatibility 
antigen induced an immunologic response at the sites of genetic 
modification. This response included a granulomatous mononuclear cell 
infiltrate beginning 10 days after introduction of the recombinant gene. 
This response resolved by 75 days after gene transfer; however, a specific 
cytolytic T cell response against the HLA-B7 molecule was persistent. 
This study demonstrated that a specific immunologic response could be 
induced by the introduction of a foreign recombinant gene at a specific 
site in vivo. Moreover, this provided one of the first indications that direct 
gene transfer of specific recombinant genes could elicit an immune 
response to the product of that gene in vivo (39). 
These studies suggested that the introduction of the appropriate 
recombinant genes could be used to stimulate the immune system to 
recognize its product in vivo. In addition, this approach provided a 
general method for the induction of a specific site in vivo. To determine 
whether direct gene transfer might be appropriate for the treatment of 
disease, a murine model of malignancy was developed. Direct gene 
transfer of an allogeneic histocompatibility complex gene into a murine 
tumor elicits an immune response not only to the foreign MHC gene but 
also to previously unrecognized tumor-associated antigens. These 
immune responses are T cell-dependent, and these tumor-associated 
proteins are recognized within the context of the self major 
histocompatibility complex. In animals presensitized to a specific MHC 
haplotype, direct gene transfer into established tumors could attenuate 
tumor growth or, in some cases, lead to complete tumor regression (40). 
These studies demonstrate that direct gene transfer of foreign MHC genes 
into tumors have potentially therapeutic effects that may be appropriate 
for the treatment of malignancy. 
In 1993, the first human clinical trial using direct gene transfer was 
initiated. Gary J. Nabel, M.D., Ph.D. and colleagues at the University of 
Michigan working with a drug produced under controlled conditions by 
Vical Incorporated, are investigating a novel molecular genetic 
intervention for human malignancy that enhances the immune response 
to tumors by in vivo gene transfer. This immunotherapeutic approach 
based on the animal model work described above (39, 40) uses a gene 
encoding a transplantation antigen, an allogeneic class I major 
histocompatibility complex (MHC) antigen, HLA-B7, with (1-2 
microglobulin introduced into human tumors in vivo by DNA/lipid 
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Recombinant DNA Research, Volume 20 
