Seattle (12), designated GIN, to follow the fate of tumor 
infiltrating lymphocytes (TIL) isolated from cancer 
patients and reinfused after expansion and vector marking 
ex vivo. These data, which have been published (11), 
have shown that the marking of the TIL cells with the NEO 
vector does not change the phenotype of the cells, does 
not result in horizontal infection, and was successful in 
tracking the fate of the marked cells. 
Subsequent clinical investigations carried out by the NIH 
have shown that the same marking vector, when carrying 
the adenosinedeaminase gene (ADA) , may result in a 
conversion of the phenotype of immunoincompetence to 
immunocompetence in severe combined immunodeficiency 
patients and results in no other adverse effects. This 
same series of marking vectors has been studied in over 
1500 mice, 21 primates (32 monkey years) , and over 70 
human patient months and has shown no adverse effect.' 
Twenty-one monkeys infused with the LNL6 marked 
autologous marrow have remained without problems for 2.5 
to 5 years. No reverse transcriptase assays have been 
positive after infusion of the marked marrow in primates 
or man. Four animals, which were exposed to a 
replication competent variant of the LNL6 vector, have 
remained negative for N2 virus 2-3 year after exposure. 
No leukemias, lymphomas, solid tumors, or other problems 
have been identified as late complications in these 
experiments which have utilized safety modified viruses 
which are replication incompetent, involve single 
transductions, and are not contaminated with replication 
competent before virus. The NIH group has recently 
reported the occurrence of thymic lymphomas in 3 of 11 
monkeys who were infected with a virus preparation which 
was purposely contaminated with a replication competent 
retrovirus (see Appendix F) . All authorities agree that 
the complication of lymphoma is attributable to the 
presence of the proliferating helper virus and perhaps 
also to the practice these workers followed of 
transducing the producer cell lines used to generate the 
virus multiple times to raise viral titres. The then 
director of the NIH, Dr. James Wyngaarden, has concluded 
in an official analysis of this issue, that the LNL6 
retroviral vector poses no health hazard and is suitable 
for use in human subjects as well as in laboratory work 
(13, 14) (see Appendix B) . 
Our own data have indicated that 3% of hematopoietic 
progenitors, measurable by in vitro colony assay, after 
vector exposure, contain the marking vector. Similar 
data has been developed in other laboratories. We have 
assessed the efficiency of transduction of the safety 
modified retroviruses LNL-6 and GINA into normal and 
leukemic hematopoietic cells. Three to ten percent of 
normal progenitor cells, which can be measured by the 
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