3.0 PROTOCOL SCHEMA 
Harvest Skin. Establish and Expand Fibroblast Line 
Transduce and Expand 
Insert IL-12 gene, select with G418, and expand 
IL-12 Elisa and Bloassav 
Activity in culture supernatant 
when cell population reaches 1 X 10' 
Harvest 
up to 5 X 10^ Fibroblasts 
Prepare Injection 
5000 rads 
First Iniectlon-dav o 
2 sites: Injection sites will be marked by Indian Ink 
Treatment site : Fibroblasts transduced with the IL-12 genes 
(Number of the fibroblasts will be adjusted to achieve the desired total 
amount of IL-12 secretion*) 
Control site: Nontransduced fibroblasts 
(The same number with transduced fibroblasts) 
Second Iniectlon-dav 7 
Same procedures as the first Injection without control fibroblast injection 
Injection sites will be examined at this visit 
Third Iniectlon-dav 14 
Same procedures as the second injection 
Fourth Iniection-dav 21 
Same procedures as the first injection 
Physical Examination and Biopsy-day 28 
One or multiple sites will undergo biopsy 
Clinical and Radiographic Assessment-day 60 and 90 
*: Total dose of IL-12 will be 10 ng/24 hours initially for the first three 
patients. After evaluation of adverse effect of initial three patients, the 
amount will be Increased to 30 ng/2A hours. This sequence will be followed to 
100, 300, 1,000, and 3,000 ng/24 hours. All three patients will need to be 
followed for at least two weeks after the previous dosage and judged to be 
without significant toxicity before escalating to the next dosage. 
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Recombinant DNA Research, Volume 19 
