did not appear to be long lived since by four weeks after immunization 
approximately 50% of mice developed tumors. This tumor immunization appeared 
to be tumor specific in that other syngeneic tumors grew normally when 
injected into these immunized mice. Of particular interest to the current 
clinical protocol was the demonstration that the injection of IL-2 transfected 
tumor cells could result in the generation of systemic cytolytic T cells 
directed against the parental tumor line. The subcutaneous injection of 
cultured unmodified tumor cells was not capable of eliciting detectable 
cytolytic T cell activity even after secondary in vitro stimulation. Fearon et 
al. also demonstrated the increased immunogenic ity of a syngeneic murine 
melanoma transduced with the IL-2 gene. It thus appeared from this work that 
the expression of an IL-2 gene and of the subsequent secretion of IL-2 by 
these syngeneic tumors resulted in a substantial increase in their 
immunogenicity and their ability to immunize animals against parental tumor 
antigens . 
The expression of IL-2 genes by tumors was further studied by 
Gansbacher, et al. who used retroviral vectors to insert the IL-2 gene into a 
weakly immunogenic mouse fibrosarcoma line (21). The secretion of IL-2 from 
the tumor cells again abrogated their tumorigenicity and induced a long 
lasting immunity against a challenge with the unmodified parental fibrosarcoma 
cancer cells. These workers also demonstrated that injection of these IL-2 
producing cells produced persistently high levels of tumor specific T cell 
mediated cytolytic activity for over two months. Thus these workers also 
demonstrated that IL-2 secretion by tumor cells was associated with a 
substantial increase in immunogenicity of syngeneic murine tumors with the 
generation of cytolytic T cells directed against these tumors. 
We have confirmed, in our own laboratory, that the retroviral mediated 
transduction of the IL-2 gene into murine tumors substantially increases their 
immunogenicity. Introduction of the IL-2 gene into the immunogenic MCA-205 
sarcoma substantially reduced its ability to form tumors in syngeneic mice in 
accord with results of the other investigator discussed above. This 
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Recombinant DNA Research, Volume 15 
