항암 면역요법제 인터루킨-2의 면역과민반응 평가연구

Potential Hypersensitivity of Recombinant Mouse IL-2 as a Immunotherapeutic Agent of Cancer in Tumor-bearing BALB/c Mice

Interleukin-2 (IL-2), a glycoprotein mainly secreted by CD4+ T helper Iymphocytes, has been developed to use recombinant cytokine to augment the immune response against cancer since IL-2 not only stimulates T Iymphocytes but also enhances natural killer (NK) cell activity. In order to evaluate the immunological safety of recombinant mouse IL-2 (rmIL-2) in cancer therapy, renal cell carcinoma was established in the flank by s.c. injection of renca cell line. Tumor-bearing BALB/c mice were treated with I.p. injections with 2×10 5 Lu rmIL-2. Even though the tumor size was diminished, there were not significant recovery of body and relative lymphoid organ weights including thymic atrophy in rmIL-2 immunotherapy. Distribution ratios of T cell subsets in thymus were analysed using flow cytometry. Without regard to dosage of rmIL-2, the ratio of CD3+CD4-CD8- T cells was increased in accordance with survival of solid tumor but that of CD4+CD8+ T cells was decreased dramatically. Emergence of autoantibodies (ANA, anti-dsDNA, and anti-histone) in blood was measured after rmIL-2 treatment. The results showed that the levels of ANA and anti-dsDNA did not significantly changed, but the level of anti-histone was increased significantly owing to rmIL-2 therapy. These results indicate rmIL-2 immunotherapy is to induce the autoimmune potential, and the anti-histone measurement as a biomarker of autoimmunity is useful in cancer immunotherapy.