CD40-activated human B cells: An alternative source of highly efficient antigen presenting cells to generate autologous antigen-specific T cells for adoptive immunotherapy
CD40-activated human B cells: An alternative source of highly efficient antigen presenting cells to generate autologous antigen-specific T cells for adoptive immunotherapy
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DOI：
10.1172/jci119822
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发表时间：
1997-12-01
影响因子：
15.9
通讯作者：
Nadler, LM
中科院分区：
文献类型：
--
作者：
Schultze, JL;Michalak, S;Nadler, LM
多项临床试验已经显示过继转移的同种异体抗原特异性T细胞用于治疗病毒感染和复发性血液恶性肿瘤的功效。相比之下，自体抗原特异性T细胞的治疗潜力尚未建立，因为在技术上难以离体产生足够数量的这些T细胞。这一目标成功的主要障碍来自于我们不能简单快速地分离和/或扩增大量高效的抗原呈递细胞（APC）用于体外抗原特异性T细胞的重复刺激。我们发现，自体CD 40激活的B细胞代表了一种容易获得的高效APC来源，其似乎具有优于其他APC的几个重要优点，用于离体T细胞扩增，包括：（a）方法简单，需要从仅50 cm（3）的外周血连续产生大量APC而不丧失APC功能;（B）诱导高峰T细胞增殖和干扰素-γ产生而不产生IL-10的能力;（c）易于冷冻保存;和（d）显著降低的成本。因此，我们认为，CD 40活化的B细胞是一种高效APC的替代来源，可用于体外产生抗原特异性T细胞，用于自体过继免疫治疗。
Multiple clinical trials have shown the efficacy of adoptively transferred allogeneic antigen-specific T cells for the treatment of viral infections and relapsed hematologic malignancies. In contrast, the therapeutic potential of autologous antigen-specific T cells has yet to be established since it has been technically difficult to generate sufficient numbers of these T cells, ex vivo. A major obstacle to the success of this objective derives from our inability to simply and rapidly isolate and/or expand large numbers of highly efficient antigen presenting cells (APCs) for repetitive stimulations of antigen-specific T cells in vitro. We show that autologous CD40-activated B cells represent a readily available source of highly efficient APC that appear to have several important advantages over other APCs for ex vivo T cell expansion including: (a) methodological simplicity necessary to generate continuously large numbers of APCs from just 50 cm(3) of peripheral blood without loss of APC function; (b) capacity to induce high peak T cell proliferation and interferon-gamma production without IL-10 production; (c) ease in cryopreservation; and (d) markedly reduced cost. We, therefore, contend that CD40-activated B cells are an alternative source of highly efficient APCs with which to generate antigen-specific T cells ex vivo for autologous adoptive immunotherapy.