演題抄録

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開催概要
開催回
第56回・2018年・横浜
 

悪性胸膜中皮腫に対する新規治療法開発を目指した前臨床研究

演題番号 : PD22-1

[筆頭演者]
演者)西岡 安彦:1 
[共同演者]
阿部 真治:2、金子 美華:3、三橋 惇志:1、大塚 憲司:1、後東 久嗣:1、加藤 幸成:3

1:徳島大学・呼吸器・膠原病内科、2:徳島大学・臨床薬学実務教育学、3:東北大学・抗体創薬研究分野

 

Malignant pleural mesothelioma (MPM) is a rare aggressive neoplasm that is associated with asbestos exposure. Despite multidisciplinary therapy, survival remains poor. Here we show three preclinical approaches to develop novel therapeutic antibody and effective combined therapies in mouse model. We have focused on podoplanin (PDPN) as a target of antibody, which is a cell surface antigen highly expressed on mesothelioma as well as glioblastoma. NZ-1 is a rat anti-human PDPN antibody showing high affinity and antibody-dependent cellular cytotoxicity. NZ-12, a rat-human chimeric antibody clearly demonstrated profound anti-tumor activity in orthotopic xenograft model of human mesothelioma cells in SCID mice. Combination of NZ-12 with chemotherapy significantly enhanced progression of mesothelioma. More promising approach to generate cancer-specific monoclonal antibody against PDPN is in progress. In addition, clinical trials including anti-angiogenic therapy and immunotherapy have been going on. To enhance the efficacy of these trials, analyzing mechanisms involved in the resistance and synergism could be important. Recently, we investigated the resistant mechanism to bevacizumab, which was centrally medicated by accumulation of fibrocytes into tumors. Inhibition of migration of fibrocytes retrieved antiangiogenic and anti-tumor property of bevacizumab, suggesting the future combination therapy. Regarding checkpoint inhibitors, combination immunotherapy with chemotherapy and anti-PD-1 antibody have been expected in clinical trials. Our study indicated that chemotherapy targeting to myeloid derived suppressor cells may be critical in combination with checkpoint inhibitors. These results suggest that further analysis in preclinical study may contribute to the development of novel effective therapy for MPM.

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