The flowsheet demonstrating the studies carried out for each patient, a copy of the Certificate of 
Analysis - N2 Retroviral Supernatant, a copy of the Certificate of Analysis - -Transduced TIL 
and the flowsheet followed in growing the transduced human TIL are shown In Appendix 
N 2/TIL. All the original data are provided to, and reviewed by, the FDA. 
A summary of the safety data: 1) there have been no side effects or toxic reactions due to the 
gene transfer; 2) there has been no evidence of replication-competent virus in any retroviral 
supernatant used for clinical studies; 3) there have been no consistent differences in the 
pattern of cell growth, phenotype or cytotoxic function in any preparation of gene-transduced 
TIL; 4) no lymphocyte population has developed IL-2 independence; and 5) there has been no 
evidence of viral exposure for any of the 8 patients based on Western analysis as well as 3T3 
amplification with S+L- of patient serum. In short, the data acquired to date (70 patient- 
months) have demonstrated no abnormalities, side effects, toxicities, or pathology due to the 
retroviral-mediated gene transfer procedure. 
1 .5.5 Assessment of the Safety of Retroviral-mediated Gene Transfer In Rhesus 
Monkeys and Humans 
Nine monkeys that have received replication-competent murine amphotropic retrovirus have 
been followed for several years (a total of 32 monkey-years). Copies of the manuscript 
entitled “Amphotropic Murine Leukemia Retrovirus is Not an Acute Pathogen for Primates” 
have been made available to the Committee. At this time, there has been no pathology, 
malignancy, toxicity, or other abnormality that could be attributed to the retrovirus (not 
retroviral vector in this case but rather infectious virus) exposure except for transient 
retroviremia in one monkey. Retrovirus exposure is confirmed by the presence of an antibody 
response to the virus with ongoing positive Western analyses in several animals. 
The conclusion from the monkey data is that, even though the long-term risk assessment is still 
to be determined, there is no detectable short-term pathology or illness caused by exposure of 
non-human primates to replication competent murine amphotropic retrovirus. 
Since foreign DNA is inserted randomly into the genome of cells that are re-infused into the 
patient, there is some potential for the insertional event to result in an unfavorable outcome. If 
the insertion disrupts a gene essential for maintaining cell function, that particular cell might 
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