Antibody-mediated B-cell depletion before adoptive immunotherapy with T cells expressing CD20-specific chimeric T-cell receptors facilitates eradication of leukemia in immunocompetent mice
Antibody-mediated B-cell depletion before adoptive immunotherapy with T cells expressing CD20-specific chimeric T-cell receptors facilitates eradication of leukemia in immunocompetent mice
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DOI：
10.1182/blood-2009-08-232967
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发表时间：
2009-12-24
期刊：
影响因子：
20.3
通讯作者：
Press, Oliver W.
中科院分区：
文献类型：
--
作者：
James, Scott E.;Orgun, Nural N.;Press, Oliver W.
我们已经建立了白血病免疫治疗的模型，使用表达嵌合T细胞受体（cTCR）的T细胞靶向正常和肿瘤B细胞上表达的CD 20分子。转移到人CD 20（hCD 20）转基因小鼠后，cTCR（+）T细胞显示出抗原特异性延迟从肺中排出，同时伴有T细胞缺失。在hCD 20转基因小鼠中，很少有cTCR（+）T细胞到达骨髓（BM），从而排除了抗白血病的有效性。在过继性T细胞治疗之前，抗hCD 20抗体介导的B细胞耗竭允许小鼠CD 20特异性cTCR（+）T细胞从肺中排出，增强T细胞存活，并促进cTCR（+）T细胞依赖性消除已建立的小鼠CD 20（+）白血病。此外，CD 20特异性cTCR（+）T细胞消除了单克隆抗体难以消除的残留B细胞。这些研究结果表明，抗体治疗，消耗抗原表达正常组织与过继性T细胞免疫治疗的组合增强了cTCR（+）T细胞的生存和控制肿瘤的能力。（血。2009; 114：5454-5463）
We have established a model of leukemia immunotherapy using T cells expressing chimeric T-cell receptors (cTCRs) targeting the CD20 molecule expressed on normal and neoplastic B cells. After transfer into human CD20 (hCD20) transgenic mice, cTCR(+) T cells showed antigen-specific delayed egress from the lungs, concomitant with T-cell deletion. Few cTCR(+) T cells reached the bone marrow (BM) in hCD20 transgenic mice, precluding effectiveness against leukemia. Anti-hCD20 antibody-mediated B-cell depletion before adoptive T-cell therapy permitted egress of mouse CD20-specific cTCR(+) T cells from the lungs, enhanced T-cell survival, and promoted cTCR(+) T cell-dependent elimination of established mouse CD20(+) leukemia. Furthermore, CD20-specific cTCR(+) T cells eliminated residual B cells refractory to depletion with monoclonal antibodies. These findings suggest that combination of antibody therapy that depletes antigen-expressing normal tissues with adoptive T-cell immunotherapy enhances the ability of cTCR(+) T cells to survive and control tumors. (Blood. 2009; 114: 5454-5463)