演題詳細

ポスター / Poster

ポスター 47 (Poster 47) :細胞療法

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日程
2013年10月11日(金)
時間
16:50 - 17:50
会場
ポスター会場 / Poster (ロイトン札幌 3F エメラルドABCD)
座長・司会
三浦 康生 (Yasuo Miura):1
1:京都大学医学部附属病院 輸血細胞治療部
 
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Tumor targeting using T-lymphocytes with an anti-CD19 chimeric antigen receptor for B cell lymphoma

演題番号 : PS-1-355

塚原 智典 (Tomonori Tsukahara):1,2、大嶺 謙 (Ken Ohmine):2,3、内堀 亮介 (Ryosuke Uchibori):1,2、井戸 寛之 (Hiroyuki Ido):2、卜部 匡司 (Masashi Urabe):1、水上 浩明 (Hiroaki Mizukami):1、久米 晃啓 (Akihiro Kume):1、中村 正孝 (Masataka Nakamura):4、Isabelle Riviere:5、Michel Sadelain:5、Renier Brentjens:5、小澤 敬也 (Keiya Ozawa):1,2,3

1:Div.Gene Therap., Ctr for Mol Med., Jichi Med. Univ., Japan、2:Div. Immunol-gene & Cell Therap., Jichi Med., Univ., Japan、3:Div. Hematol., Jichi Med., Univ., Japan、4:Human Gene Sci Ctr., Tokyo Med. & Dent. Univ., Japan、5:Memorial Sloan Kettering Cancer Center, USA

 

For the treatment of refractory B-cell non-Hodgkin lymphoma, we conducted experiments to develop an adoptive immunotherapy using genetically engineered autologous T lymphocytes that express a CD19-antibody fragment fused to the TCRz/CD28 receptor (19-28z). Here we examined whether 19-28z-transduced T lymphocytes could eradicate CD19+ tumors in vitro and in mouse xenograft models. Human peripheral blood T lymphocytes from healthy volunteers were activated by immobilized anti-CD3 antibody/Retronectin, and transduced with retrovirus vectors encoding 19-28z prepared from producer cells, established by stable transduction of the 19-28z plasmid into the PG13 packaging cells. Transduced T lymphocytes were expanded ex vivo in the presence of NIH3T3 fibroblasts expressing human CD19. Following CD19 antigen stimulation, 19-28z-transduced cell numbers increased about 200-fold, and the surface expression of 19-28z positive CD3+ T lymphocytes was approximately 75%, as assessed by flow cytometry. These T lymphocytes also produced IL-2 and IFNγ in response to antigen stimulation. Expanded 19-28z+T lymphocytes lysed CD19+ tumor cell lines (Raji and Daudi burkitt lymphoma cell lines) in 51Cr release assays. Immunohistochemistry revealed that 19-28z+T lymphocytes were efficiently localized to Raji tumors, and infused such T lymphocytes suppressed Raji tumor progression in SCID mice as assessed by in vivo imaging. These results indicate that functional 19-28z+T lymphocytes would be effective for the treatment of refractory B-cell non-Hodgkin lymphoma.

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