RISKS AND DISCOMFORTS 
This study may involve the following risks and/or discomforts: 
Risks Associated with ACN53 Gene Therapy 
Risks associated with gene therapy of liver tumors using the modified virus carrying the 
p53 gene are largely unknown. It is possible that I may experience the following 
complications or side-effects of the gene therapy: 
1 . Although the virus that is being used has been modified so that it cannot grow or 
multiply, it is possible that during the study the virus will somehow acquire the 
ability to reproduce itself. If this does occur, the consequences are not known with 
certainty. However, since unmodified adenovirus is known to be safe and not 
typically associated with disease beyond the common cold, it is unlikely that serious 
complications will occur if the modified virus does reproduce. 
2 . The modified virus may spread to others, particularly if it acquires the ability to 
reproduce itself. This is considered highly unlikely since the virus is being 
administered internally, thus making it difficult for the virus to escape into the 
environment, and to my liver, an organ which is known to be efficient at destroying 
adenovirus. In addition, I will be monitored for virus appearing in my blood, urine, 
and stool, and will remain in the hospital until it is established that my body is not 
excreting the virus. 
3 . The modified virus may spread to my reproductive organs, and could affect an 
embryo or fetus if I am pregnant. Pregnancy excludes participation in the study and 
strict birth control is required if I am fertile. 
4 . My immune system may react to the virus. This may involve a brief allergic reaction 
and/or rapid destruction of the virus. It is possible, although unlikely, that an 
immune response with inflammation may cause significant injury within my liver or 
surrounding tissues. It is more likely that any inflammation will be limited and 
temporary. The response of my immune system to the treatment is one of the areas 
which is being evaluated in this study. 
5 . The modified virus may cause injury to my liver or other surrounding tissues. In 
addiuon to the possibility of serious inflammadon caused by the virus, the treatment 
may cause injury if the gene therapy is harmful to normal cells, by introducing to 
them higher than normal levels of the p53 gene. However, experiments have failed 
to show that this occurs. 
6. The study will involve increasing doses of the modified virus. The lowest dose of 
virus will be studied in three padents before the next (higher) dose is used, and this 
dose will be studied in three padents before the next (higher) dose is used, and so 
on. The effects of different doses is another of the areas which is being evaluated in 
this study. Since padents will be assigned to different doses, it is likely that some 
padents will receive low doses which are too small to cause any beneficial effects. 
In addiuon, some padents will receive higher doses which may cause increased side 
effects. At this time, the chance that side effects may occur with a particular dose 
cannot be accurately predicted. It is common with more tradidonal and-cancer drugs 
that higher doses are more likely to cause side -effects. 
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Recombinant DNA Research, Volume 20 
