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

Cho, Young-Joo (Department of Toxicology, National Institute of Toxicological Research, Korea Food Drug Administration)
Eom , Juno H. (Department of Toxicology, National Institute of Toxicological Research, Korea Food Drug Administration)
Gil , Jung-Hyun (Department of Toxicology, National Institute of Toxicological Research, Korea Food Drug Administration)
Park , Jae-Hyun (Department of Toxicology, National Institute of Toxicological Research, Korea Food Drug Administration)
Lee , Jong-Kwon (Department of Toxicology, National Institute of Toxicological Research, Korea Food Drug Administration)
Oh , Hye-Young (Department of Toxicology, National Institute of Toxicological Research, Korea Food Drug Administration)
Park , Kui-Lea (Department of Toxicology, National Institute of Toxicological Research, Korea Food Drug Administration)
Kim , Hyung-Soo (Department of Toxicology, National Institute of Toxicological Research, Korea Food Drug Administration)
Publication Information
YAKHAK HOEJI / v.48, no.6, 2004 , pp. 335-344 More about this Journal
Abstract
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 $2{\times}10^5$ 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.
Keywords
IL-2; cancer in immunotherapy; autoantibody; flow cytometry;
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