DECREASED TUMORIGENICITY OF A TRANSPLANTABLE RAT SARCOMA FOLLOWING TRANSFER AND EXPRESSION OF AN IL-2 CDNA

The notion that tumour-cell-derived IL-2 might lead to paracrine stimulation of the host anti-tumour response was tested in a transplantable rat sarcoma model. Three HSNLV clones induced to secrete different amounts of human IL-2 following retroviral gene transfer showed reduced tumorigenicity and metastatic potential in athymic (nu/nu) and immunocompetent syngeneic rats which was directly related to the level of IL-2 secretion. In contrast, the tumorigenicity of HSNLV clones secreting a biologically inactive form of IL-2 (IL-2Lys20) was unaltered. T-lymphocyte-mediated rejection of ZIP I, the highest IL-2 producer, was demonstrated histologically in hooded rats and infiltrating mononuclear cells were also observed in Zip I tumours growing in athymic rats. Tumours derived from IL-2-secreting HSNLV showed reduced or absent IL-2 secretion in immunocompetent rats, sometimes with associated loss of the IL-2 provirus, but continued to secrete IL-2 in nude rats. The host response to Moloney-helper-virus-infected HSNLV was also examined and the results represent a cautionary note to those undertaking experiments of a similar nature.