Antitumor reactivity of anti-CD3/anti-CD28 bead-activated lymphoid cells: Implications for cell therapy in a murine model
Antitumor reactivity of anti-CD3/anti-CD28 bead-activated lymphoid cells: Implications for cell therapy in a murine model
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DOI：
10.1097/00002371-200305000-00006
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发表时间：
2003-05-01
影响因子：
3.9
通讯作者：
Li, Q
中科院分区：
文献类型：
--
作者：
Ito, F;Carr, A;Li, Q
通过mAb连接T细胞上表达的TCR和CD 28导致能够在过继免疫治疗中破坏肿瘤的T细胞的活化。在鼠模型中，作者使用与CD 3和CD 28结合的平板固定和珠缀合mAb检查了体外活化条件。与平板活化的细胞相比，珠活化的肿瘤引流淋巴结（TDLN）细胞表现出上级细胞因子（IFN-γ、GM-CSF、IL-2和IL-10）分泌，并更有效地介导肿瘤消退。与平板活化的细胞相比，珠活化的TDLN细胞具有显著更高的CD 4（+）细胞百分比。在每个细胞的基础上，阳性选择的CD 4（+）细胞激活珠偶联或板固定的单克隆抗体介导的肿瘤特异性消退相同。与平板活化的CD 4（+）细胞相比，珠活化的CD 4（+）TDLN细胞显示出显著更高水平的肿瘤特异性IL-2分泌，后者可能为CD 8（+）效应细胞提供辅助功能。珠激活的淋巴样细胞的抗肿瘤反应性取决于它们的来源。珠粒活化后的TDLN细胞在体内介导肿瘤消退方面比来自荷瘤宿主的脾细胞更有效。来自非肿瘤宿主的珠粒活化LN细胞和脾细胞在过继免疫治疗中表现出非特异性细胞因子分泌和最小功效。在最小剂量的IL-2，珠活化的TDLN细胞的抗肿瘤反应性显着增强。肿瘤致敏T细胞的抗CD 3/抗CD 28珠活化代表了产生用于免疫治疗的效应细胞的有效方法。
Ligation of TCR and CD28 expressed on T cells via mAbs results in activation of T cells capable of tumor destruction in adoptive immunotherapy. In a murine model, the authors examined in vitro activation conditions utilizing plate-immobilized and bead-conjugated mAbs that bind to CD3 and CD28. Bead-activated tumor-draining lymph node (TDLN) cells demonstrated superior cytokine (IFN-gamma, GM-CSF, IL-2, and IL-10) secretion and mediated tumor regression more efficiently compared with plate-activated cells. The bead-activated TDLN cells had a significantly higher percentage of CD4(+) cells compared with plate-activated cells. On a per-cell basis, positively selected CD4(+) cells activated with bead-coupled or plate immobilized mAbs mediated tumor-specific regression equally. Bead-activated CD4(+) TDLN cells demonstrated significantly higher levels of tumor specific IL-2 secretion compared with plate-activated CD4(+) cells that may provide helper function to CD8(+) effector cells. The antitumor reactivity of bead-activated lymphoid cells depended upon their source. TDLN cells after bead activation were more potent than splenocytes from tumor-bearing hosts in mediating tumor regression in vivo. Bead-activated LN cells and splenocytes from nontumor-bearing hosts demonstrated nonspecific cytokine secretion and minimal efficacy in adoptive immunotherapy. At minimal doses of IL-2, the antitumor reactivity of bead-activated TDLN cells was significantly enhanced. Anti-CD3/anti-CD28 bead activation of tumor-primed T cells represents an efficient method to generate effector cells for immunotherapy.