IMMUNOLOGICAL MEMORY INDUCED BY GENETICALLY TRANSDUCED TUMOR-CELLS

Background: Recent studies have demonstrated the usefulness of gene-mo dified tumor cells for immunotherapy. Using the tumorigenic murine fib rosarcoma, MCA 106, we investigated the effects of localized interfero n-gamma (IFNg) secretion on tumorigenicity and on longterm memory. Met hods: The murine IFNg (MuIFNg) gene was introduced into tumor cells. H igh and low IFNg-secreting clones were isolated. C57BL/6 mice were inj ected subcutaneously (s.c.) with either parental (P), high or low IFNg -secreting (H- or L-IFNg) cells, and tumor growth was assessed weekly. Spleens were harvested on different days postinjection (p.i.) to asse ss in vitro cytolytic activity. In parallel, tissues from injection si tes were stained with macrophage-, CD4-, and CD8-detecting antibodies. Mice were injected s.c. with H-IFNg MCA106 tumor. After 150 days the animals were rechallenged s.c. with MCA106P in one leg and with irrele vant syngeneic tumor in the other. Results: Both P- and L-IFNg cells h ad similar growth, whereas the H-IFNg cells never grew. Only splenocyt es from the H-IFNg animals showed in vitro CTL activity persisting unt il day 30 p.i. Histological data revealed a macrophage and CD4(+) infi ltrate much earlier in the H-IFNg group compared with the P group, Onl y the irrelevant, syngeneic tumor grew in animals previously injected with H-IFNg cells, whereas both P and irrelevant syngeneic tumors grew in controls.Conclusions: Transduction of MCA106 cells with the MuIFNg gene diminished in vivo tumorigenicity in proportion to the amount of IFNg secreted. Immunization with H-IFNg cells elicited a host respons e characterized by macrophages and CD4(+) cells. Long-term tumor-speci fic memory was seen after immunization with H-IFNg cells.