TNF administration can also be associated with side effects including fever, 
chills, hypotension, oliguria, weight loss, nausea, vomiting and malaise. 
All side effects will be graded using the standard toxicity sheet used in 
all prior IL-2 related protocols presented in Appendix B. 
4. Potential risks of retroviral mediated gene modification of TIL (29) . 
1) Insertional mutagenesis . The Moloney murine leukemia virus used 
in this vector construct can cause T cell lymphomas in certain strains of mice. 
The possibility of causing malignancy in cells secondary to the random 
insertion of the retroviral vectors in the genome exists, though the actual 
'risk of this occurring is thought to be low. 
The design of the proposed protocol, however. Includes time for extensive 
testing of TIL following exposure to the retroviral vector prior to Infusion 
into the patient. Tests of the viral supernatant as well as of the actual TIL 
used for infusion will be conducted to assure that no replication competent 
virus is present in either preparation. In addition, tests will be performed 
on the transduced TIL populations themselves to assure that they remain 
dependent on IL-2 for their continued proliferation. TIL are dependent on IL-2 
for their continued growth and will die in the absence of IL-2. IL-2 will be 
withdrawn from an aliquot of the culture prior to TIL infusion to assure that 
TIL retain their dependence on IL-2. 
2) Risk from murine retrovirus. Exposure of the cancer patient to 
retrovirus could theoretically pose a risk of insertional mutagenesis. It 
should be emphasized, however, that careful tests will be conducted to assure 
that the patient is not exposed to replication competent virus. The retrovirus 
derived from the Moloney murine leukemia virus has been modified so that it no 
longer contains any intact viral genes and thus cannot produce the envelope 
proteins necessary to package its RNA into an intact infectious virus 
(22,23,30,31). To assemble the retrovirus, a retrovirus packaging cell line 
Recombinant DNA Research, Volume 14 
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