演題抄録

臓器別シンポジウム

開催概要
開催回
第51回・2013年・京都
 

成人T細胞白血病/リンパ腫(ATL)治療の進歩

演題番号 : OS18-4

[筆頭演者]
鵜池 直邦:1 
[共同演者]
飯野 忠史:2、宇都宮 與:3、岡村 純:4、神奈木 真理:5、末廣 陽子:1、高田 豊:6、谷口 修一:7、田野崎 隆二:8、崔 日承:1、豊嶋 崇徳:9、渡辺 信和:10

1:独立行政法人国立病院機構九州がんセンター血液内科、2:九州大学先端医療イノベーションセンター、3:財団法人慈愛会今村病院分院、4:独立行政法人国立病院機構九州がんセンター小児科、5:東京医科歯科大学大学院医歯学総合研究科、6:独立行政法人国立病院機構九州がんセンター臨床研究センター、7:虎ノ門病院血液内科、8:国立がん研究センター中央病院輸血療法科、9:北海道大学大学院医学研究科、10:東京大学医科学研究所幹細胞治療研究センター

 

Evidences that adult T‐cell leukemia/ lymphoma (ATL) was an incurable peripheral T‐cell malignancy caused by human T‐cell leukemia virus type 1 (HTLV‐1) with conventional chemotherapy and that immunological therapeutic approaches such as allogeneic hematopoietic stem cell transplantation (HSCT) had been shown to be effective made us notice vulnerability of ATL cells against immune attacks. We organized prospective clinical studies for effects of HSCT by non-myeloabrative conditioning for elderly patients and, further, those of cell therapy using autologous dendritic cells (DC) for already treated patients with ATL. Reduced intensity conditioning regimen (RIC) have been adopted to patients of 50~65-year old, at first, with adequate related donors and then with unrelated donors from Japan Marrow Donor Program, and at last, with unrelated umbilical cord blood. Immunological examinations during the HSCT studies activation of CD8+ Tax-specific cytotoxic T-lymphocytes (CTL) observed in ATL patients following HSCT suggests that not only allogeneic immune rections but also potential contributions of the CTL effects to the HTLV-1 virus itself were involved. We developed an anti-ATL therapeutic vaccine consisting of autologous DCs pulsed with Tax peptides of HTLV-1 corresponding to the major epitopes of Tax-specific CTL previously identified from HLA-A2, A24 or A11-possessing post-HSCT ATL patients. We conducted the phase-I study of the anti-ATL immunotherapy for previously treated ATL patients at stable disease conditions. The peptide-pulsed DCs were subcutaneously injected for three times at 2-week intervals. Three acute type patients completed the course of the study without severe side effects except for fever and skin rash. One of the patients showed a significant reduction in the proviral loads and achieved PR, suggesting the safety and promising effects of the vaccine therapy for ATL.

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