Antitumor Effects of 5′‐Deoxy‐S‐fluorouridine in Combination with Recombinant Human Interleukin 2 on Murine Colon Carcinoma 26

The antitumor activity of rccombinant human interleukin 2 (rIL‐2) in combination with 5′‐deoxy‐5‐fluorouridine (doxifluridine; 5′‐DFUR) against murine colon carcinoma 26 (Colon 26) was studied. BALB/c mice were treated daily for 15 days with S'‐DFUR, rIL‐2 or both, beginning on day 7 after subcutaneous transplantation of Colon 26. While mice treated with 5′‐DFUR or rIL‐2 alone died of tumor growth with pulmonary metastases within 9 weeks posttransplantation, the survival time was significantly prolonged in mice treated with both 5′‐DFUR and rIL‐2. Most of the combination‐treated animals showed the regression of local tumors and the inhibition of pulmonary metastasis. Histopathologically, many tumor cells were degenerated and necrotized, with marked infiltration of mononuclear cells including large granular lymphocytes (LGLs) with periodic acid‐Schiff‐positive cytoplasmic granules. The cells were positive for CD3s, asialo GM1 and NK1.1. Spleen cells from the combination‐treated mice showed high activities of natural killer (NK) cytotoxicity as well as growth inhibition of Colon 26 and Meth A fibrosarcoma in mice. The results suggest that the combination therapy of 5′‐DFUR plus rIL‐2 enhanced non‐specific cytotoxicity of LGL/NK cells for Colon 26 in tumor‐bearing mice and was effective in the inhibition of tumor growth.