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 tumorige‐nicity 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.