ANTITUMOR EFFECTS OF 5'-DEOXY-5-FLUOROURIDINE IN COMBINATION WITH RECOMBINANT HUMAN INTERLEUKIN-2 ON MURINE COLON-CARCINOMA-26

The antitumor activity of recombinant human interleukin 2 (rIL-2) in c ombination with 5'-deoxy-5-fluorouridine (doxifluridine; 5'-DFUR) agai nst murine colon carcinoma 26 (Colon 26) was studied. BALB/c mice were treated daily for 15 days with 5'-DFUR, rIL-2 or both, beginning on d ay 7 after subcutaneous transplantation of Colon 26, While mice treate d with 5'-DFUR or rIL-2 alone died of tumor growth with pulmonary meta stases within 9 weeks posttransplantation, the survival time was signi ficantly prolonged in mice treated with both 5'-DFUR and rIL-2. Most o f the combination-treated animals showed the regression of local tumor s and the inhibition of pulmonary metastasis. Histopathologically, man y tumor cells were degenerated and necrotized, with marked infiltratio n of mononuclear cells including large granular lymphocytes (LGEs) wit h periodic acid-Schiff-positive cytoplasmic granules. The cells were p ositive for CD3 epsilon, asialo GM1 and NK1.1. Spleen cells from the c ombination-treated mice showed high activities of natural killer (NK) cytotoxicity as well as growth inhibition of Colon 26 and Meth A fibro sarcoma in mice. The results suggest that the combination therapy of 5 '-DFUR plus rIL-2 enhanced non-specific cytotoxicity of LGL/NK cells f or Colon 26 in tumor-bearing mice and was effective in the inhibition of tumor growth.