Selective elimination of human regulatory T lymphocytes in vitro with the recombinant immunotoxin LMB-2
Selective elimination of human regulatory T lymphocytes in vitro with the recombinant immunotoxin LMB-2
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DOI：
10.1097/01.cji.0000187959.45803.0c
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发表时间：
2006-03-01
影响因子：
3.9
通讯作者：
Rosenberg, SA
中科院分区：
文献类型：
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作者：
Attia, P;Powell, DJ;Rosenberg, SA
CD 4（+）CD 25（+）调节性T细胞（T-reg）可抑制小鼠和人类中CD 4（+）CD 25（-）辅助性T细胞的增殖和细胞因子分泌。在小鼠肿瘤模型中，这些T-reg细胞的存在可以抑制T细胞转移和主动免疫方法的抗肿瘤效果。因此，我们已经开始努力从人外周血单核细胞（PBMC）中选择性地消除T-reg细胞，以潜在地支持抗肿瘤反应。LMB-2是一种重组免疫毒素，是抗Tac抗CD 25单克隆抗体的单链Fv片段与细菌假单胞菌外毒素A的截短形式的融合体。在体外孵育人PBMC与LMB-2降低了CD 4（+）CD 25（+）和Foxp 3表达细胞的水平，而不损害其余淋巴细胞的功能。LMB-2的体内半衰期较短，使其成为在给予癌症疫苗或细胞转移免疫治疗方法之前减少体内人类T-reg细胞的有吸引力的候选者。
CD4(+)CD25(+) T-regulatory cells (T-reg) can inhibit the proliferation and cytokine secretion of CD4(+)CD25(-) helper T cells in mice and humans. In murine tumor models, the presence of these T-reg cells can inhibit the antitumor effectiveness of T-cell transfer and active immunization approaches. We have thus initiated efforts to eliminate T-reg cells selectively from human peripheral blood mononuclear cells (PBMCs) to potentially bolster antitumor responses. LMB-2 is a recombinant immunotoxin that is a fusion of a single-chain Fv fragment of the anti-Tac anti-CD25 monoclonal antibody to a truncated form of the bacterial Pseudomonas exotoxin A. In vitro incubation of human PBMCs with LMB-2 reduced the levels of CD4(+)CD25(+) and Foxp3-expressing cells without impairing the function of the remaining lymphocytes. The short in vivo half-life of LMB-2 makes it an attractive candidate for reducing human T-reg cells in vivo before the administration of cancer vaccine or cell transfer immunotherapy approaches.