4.7.2 Malignancy Caused by Insertional Mutagenesis 
This is a non-trivial risk. From a theoretical standpoint, approximately four to five 
insertional events are likely required within a cell to cause malignant 
transformation^. In this case, the risk of potential malignant transformation has 
been assessed by tumorigenicity studies conducted in nude mice, 
immunosuppressed suckling mice, and transformation studies in soft agar. No 
evidence of tumor formation in the former (nude and suckling mice) or 
transformation in the latter [soft agar using cells transduced with HIV-IT (V)] has 
been observed. 
4.7.3 Contamination and/or Mutation of Germ Cells 
This risk is largely theoretical because (1) the vector is engineered to be non- 
replicating; and (2) extensive PCR analysis of male Rhesus macaque monkeys and 
HIV-1 infected chimpanzees after treatment with HIV-IT (V) has shown no transfer 
of HIV-IT (V) into the germ line tissues of these animals. 
4.7.4 Further Immune Suppression Precipitated by the Release of Active 
Infectious HIV-1 Virus From CTL-Lysed HIV-Infected Macrophages 
4.7.4. 1 The magnitude of this risk is uncertain, however, most intracellular 
HIV-1 is not infectious, and becomes infectious only after budding out 
from cell surfaces. 
4. 7. 4. 2 Clinical and laboratory parameters will be monitored for evidence of 
exacerbation of disease. 
4.7 .4. 3 CD4 + T-cell will be monitored in samples taken 2 days prior to injection 
and at each visit thereafter. Viral burden will be monitored frequently. 
4.7.5 Exacerbation of Disease Due to the Killing of Uninfected CD4 T- 
Cells as a Result of HIV-Ihib ENV Toxicity 
4.7.5. 1 The magnitude of this risk is uncertain, however, previous vaccine 
studies using HIV-1 ENV to stimulate an HJTV-1 specific antibody 
response indicate that much larger quantities of HIV- 1 ENV than are 
20 Fearon, E., and Vogelstein, B., Cell, 61:759-67 (1990). 
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Recombinant DNA Research, Volume 17 
