Combination Therapy of Colon Carcinoma 26 in Mice with Recombinant Human Interleukin-2 and Interferon-α A/D: Occurrence of Large Granular Cells in the Tumor

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Abstract
The antitumor effects of recombinant human interleukin-2 (rIL-2), in combination with recombinant human interferon-.alpha. A/D hybrid (rIFN-.alpha. A/D) on colon carcinoma 26 (colon 26) in mice were examined histologically. Colon 26 was transplanted subcutaneously into female BALB/c mice on day 0. The mice bearing the tumor received intramuscular injection of rIL-2, rIFN-.alpha. A/D or the combination of rIL-2 and rIFN-.alpha. A/D for 2-10 consecutive days starting on day 7. Mice were killed on days 9, 13, 17 and 21. After day 13, growth of the tumor was significantly suppressed in the mice treated with rIL-2 or rIFN-.alpha. A/D alone and was stopped in the mice treated with rIL-2 in combination with rIFN-.alpha. A/D. Histologically, tumor necrosis developed in all treated groups, though the degree was the most severe in the group receiving combination treatment. Many large cells (about 15-30 .mu.m in diameter) infiltrated into the tumor, and they had Thy-1 surface antigen and many periodic acid-Schiff-positive round granules in the cytoplasm. The incidence of these large granular cells was correlated well with the reduction in tumor weight. The ultrastructural features of the large granular cells were very similar to those of murine large granular lymphocyte-like cells maintained in vitro in an IL-2-containing medium. The present large granular cells appear to be a kind of activated lymphoid cells.

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