@article{oai:niigata-u.repo.nii.ac.jp:00028580, author = {西澤, 幹則 and 成田, 美和子 and 岩谷, 俊平 and 大岩, 恵理 and 岩渕, 南 and 内山, 孝由 and 松山, 麻子 and 高橋, 益廣}, issue = {1}, journal = {新潟大学保健学雑誌, 新潟大学保健学雑誌}, month = {Mar}, note = {ウステキヌマブはヒト型抗ヒト interleukin(IL)-12/IL-23p40モノクローナル抗体製剤であり,乾癬の治療に用いられている。しかし,IL-12は抗腫瘍免疫において重要な役割を担うため,ウステキヌマブによる腫瘍発生率の増加が懸念されている。今回の検討では,ウステキヌマブの抗原特異的癌免疫における影響を明らかにすることを目的とした。乾癬患者に対する in vivo の検討では,ウステキヌマブの投与により乾癬症状は改善されたが,腫瘍抗原特異的細胞傷害性 T 細胞(CTL)の frequency は投与開始以降も抑制されることはなかった。また in vitro の検討では,樹状細胞の抗原提示能及び抗原特異的 CTL の誘導に対するウステキヌマブの抑制効果は確認できなかった。これらの結果から,ウステキヌマブは樹状細胞の機能や腫瘍抗原特異的 CTL の誘導を抑制することなく乾癬症状を改善することが可能であり,ウステキヌマブ治療症例における腫瘍発症の増加は見られないという最近の臨床試験の知見を支持するものと考えられた。, Ustekinumab (a humanized monoclonal antibody against the common p40 subunit shared by IL-12 andIL-23) blocks the pathways of T helper (Th)-1 and Th-17, which play pivotal roles in cell-mediated immunity and production of pro-inflammatory cytokines. Ustekinumab is currently used for the treatment of moderate to severe psoriasis with remarkable efficiency. However, worries about the development of malignancies in ustekinumab-treated patients could not be completely cleared because of the major role of IL-12 and IL-23 in tumor immunity. In the present study, we tried to elucidate the effects of ustekinumab on antigen-specific tumor immunity. A 56 years-old male volunteer was subcutaneously administered with 20 times of WT1 peptide. WT1 tetramer+ CD8+ T cells appeared after the first peptide administration and the frequency of WT1 tetramer+ T cells elevated to more than 15 in 10^6 CD8+ T cells. He began to be treated with subcutaneous injections of ustekinumab for moderate psoriasis. Psoriasis plaques were almost cleared up at week 12. The frequency of WT1 tetramer+ T cells with cytotoxic ability has not changed for 22 months since the initiation of ustekinumab treatment. The effects of ustekinumab on antigen presenting and CTL inducing abilities of dendritic cells were explored in vitro, resulting in little effects on both immune functions. These in vivo/vitro findings imply that ustekinumab improves psoriasis without suppressing tumor antigen-specific cytotoxic T lymphocytes and support the data of recent clinical trials showing a comparable incidence of malignancies between ustekinumab-treated psoriatic patients and the control.}, pages = {75--82}, title = {IL-12/IL-23p40モノクローナル抗体製剤ウステキヌマブの腫瘍抗原特異的細胞傷害性T細胞 (CTL) に対する影響}, volume = {11}, year = {2014} }