III. Response to the Stipulations of the NHL3I IR3 : 
1) Informed consent: being revised 
2) No infectious viral particles: see I.B.3.b. 
3) N2 infected cells are representative: see I.B.3.a. 
Response to the Recommendations of the NCI IR3 : 
1) Risks of horizontal viral transmission: see I.B.3.b. 
2) Packaging cell info: reprint and discussion in PCDD 
3) Assay for infectious virus: see I.B.3.b. 
4) Results of in vivo safety experiments: see I.B.3.b. 
5) Informed consent (risks): being revised 
6) Informed consent (aminoglycosides): being revised 
7) Informed consent ("safety"): being revised 
8) Informed consent (malignant potential): being revised 
9) Layperson document: being prepared 
10) Separate proposal: being considered 
V. Conclusion 
Ve believe that the data that we have obtained with human TIL, with the 
murine T cell animal model system, and with our safety studies in monkeys are 
sufficient to provide satisfactory answers for the relevant safety and efficacy 
questions raised by our protocol. Ve have shown that human TIL can be transduced 
with our N2 retroviral vector, that the transduced TIL are not fundamentally 
altered in growth rate, surface antigen phenotype, cytotoxicity, or lymphokine 
production and are, therefore, representative of the total TIL population, and 
that the transduced TIL are free of any infectious retroviruses or of packaging 
genomes. Ve have shown using the closest available animal model, namely soluble 
antigen- activated CD4 murine T lymphocytes, that N2 - transduced T cells can be 
recovered from an animal several weeks after injection and that these T cells can 
be selectively grown in culture. Finally, we have shown that our amphotropically 
packaged retroviral vectors do not appear to pose a public health risk either 
to the patient or to health care personnel since even large injections of 
infectious virus into immune -suppressed monkeys cause no apparent pathology. The 
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