In summary, the introduction and constitutive expression of IL-2 by tumor cells 
themselves has increased the immunogenicity of a variety of histologically 
different cancers. It appears from these studies that the localized, persistent 
expression and secretion of low levels of IL-2 may have an impact on the host 
anti-tumor response in the absence of any detectable toxicity. 
2.6 Gene transfer in Humans 
Most recently, Rosenberg et al have taken genetically altered autologous tumor 
infiltrating lymphocytes and injected them into patients with refractory metastatic 
tumors (17). A retroviral vector containing the neomycin-resistance gene was 
introduced into autologous lymphocytes in order to monitor cells reinfused into 
patients. Of five patients reported, cells from four were successfully grown in 
tissue cultures with G418, a neomycin analogue. These cells that showed 
neomycin resistance were given intravenously to patients along with systemic IL- 
2. Peripheral blood was recovered periodically and circulating mononuclear cells 
with neomycin resistance were detected. There were no additional toxicides seen 
as a result of the genetic alteration. No intact virus was recovered from any 
patient. Rosenberg concluded that this procedure was both feasible and safe (17). 
Prior safety studies have shown that exposure of primates to large infusion of 
infectious murine amphotrophic virus produces no acute pathologic effects (37). 
Twenty one primates transplanted with retroviral gene-modified bone marrow 
showed no evidence of toxicity related to the gene transfer as long as five years 
after infusion (35). The first adenosine deaminase-deficient patient with Severe 
Combined Immunodeficiency (SCID) underwent successful retroviral mediated 
adenosine deaminase gene transfer approximately one year ago at the NCI (35). 
So far, investigators observed partial reconstitution of cellular immune function 
after infusion without any detectable adverse effects on the patient. 
To investigate whether findings from the murine system could be extended, 
human tumor cell lines have been infected with cytokine genes using retroviral 
vectors. To date, the human IL-2 gene, human IFN -7 gene and the human 
epidermal growth factor gene have all been successfully transduced into a variety 
of human cell lines at MSKCC. In collaboration with Dr. Ray Taetle (University 
of Arizona), the epidermal growth factor receptor gene has been introduced into 
the Burkitts lymphoma cell line, Namalwa; the receptor was shown to be 
expressed on the cell surface and fully functional (36). Stimulation of these 
transduced cells with the epidermal growth factor led to the appropriate binding 
of ligand and signal transduction (36). In addition, the IL-2 or the EFN -7 gene 
have been introduced and expressed in primary and established human melanoma 
cell lines. These genetically modified human melanoma cells secreted 
constitutively up to 40 U/ml recombinant IL-2 into the supernatant. Constitutive 
IFN -7 expression led to upregulation of MHC class I and class II antigens on the 
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