CLINICAL PROTOCOL 
Product: VCL-1102 
July 7, 1994 
VICAL INC. 
9373 Towne Centre Dr., Ste. 100 
San Diego, CA 92121 
complex transfection. The direct intratumoral injection approach is used. 
Expression of allogeneic MHC antigens on tumor cells stimulates 
immunity against both the transfected cells as well as previously 
unrecognized antigens present in unmodified tumor cells. The 
introduction of an allogeneic MHC gene directly in tumors in vivo has 
induced partial tumor regressions, as well as specific cytotoxic T cell 
responses to other antigens. 
In the initial human trial. Dr. Nabel treated 5 patients with malignant 
melanoma. Three patients received 3 treatments, totaling 0.87 pg of DNA 
intratumorally, and 3 patients (2 additional patients plus one of the 
original 3 patients) received cumulative dose of 2.58 pg of DNA via three 
treatments. No toxicity resulted from this form of treatment and no 
formation of anti DNA antibody or autoantibody was noted. There was 
no plasmid DNA detectable in the blood by PCR following gene transfer 
(tested on days 3-7 post transfection at ~2 pg/mL sensitivity). 
Evidence of gene transfer was found on biopsy of the injected tumor. The 
biopsy samples were analyzed for plasmid DNA, mRNA coding for HLA- 
B7 and the expression of HLA-B7 protein. In 4 of the 5 patients, plasmid 
DNA and HLA-B7 mRNA were detected within the treated nodules by 
PCR. HLA-B7 expression was confirmed in all treated nodules by 
immunohistochemical staining with a monoclonal antibody to the gene 
product. Two patients, where cell lines were established from the tumor, 
showed an immune response by lysing autologous tumor cells. One of the 
5 patients had a partial remission which involved both cutaneous and 
visceral disease. (41). 
These data suggest that tumor cells modified with the HLA-B7 gene not 
only stimulate CTLs and potentially other immune system cells to 
recognize tumors expressing HLA-B7, but they may also provide a 
stimulus to immune cells to eliminate tumor cells at other sites which 
express tumor associated antigens in association with the patient's own 
HLA antigens. 
Based on the positive preliminary results in 5 patients. Dr. Nabel gained 
approval from the NIH Recombinant Advisory Committee and allowance 
from ti^e FDA for further testing of up to 24 cancer patients. Vical 
Incorporated, in January 1994, independently filed an Investigational New 
Drug Application with the FDA to expand the full safety assessment and 
dosing optimization of the HLA-B7-DMRTE/DOPE, DNA/lipid complex. 
The FDA allowed Vical to initiate a Phase I/EE trial at three study sites, 
with each site treating 15 patients. The Arizona Cancer Center is testing 
Recombinant DNA Research, Volume 20 
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