Dendritic cells armed with anti-CD3 mAbs reduce pulmonary metastases, prolong survival, and engender antitumor effector cells demonstrable by adoptive transfer.
Dendritic cells armed with anti-CD3 mAbs reduce pulmonary metastases, prolong survival, and engender antitumor effector cells demonstrable by adoptive transfer.
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配备抗 CD3 mAb 的树突状细胞可减少肺转移、延长生存期，并产生可通过过继转移证明的抗肿瘤效应细胞。
DOI：
10.1007/s10434-000-0771-9
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发表时间：
2000
影响因子：
3.7
通讯作者：
Suthanthiran,M
中科院分区：
文献类型：
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作者：
Maluccio,MA;Rao,J;Sharma,V;Lagman,M;Suthanthiran,M
背景：用肿瘤细胞或肽脉冲的树突状细胞（DC）在许多肿瘤模型中是有效的抗肿瘤剂。鉴于我们早期证明，通过 CD3 蛋白的 T 细胞信号传导会诱导细胞溶解活性并限制肿瘤进展，我们为用肿瘤细胞脉冲的 DC 配备了抗 CD3 mAb，并在小鼠肾细胞癌肺转移模型中测试了它们的抗肿瘤功效。 方法：我们研究了用完整照射的肿瘤细胞脉冲的 DC 的抗肿瘤功效 (DC/R) 或用经照射的肿瘤细胞进行脉冲并配备有抗 CD3 mAb 的 DC（DC/R/抗 CD3 mAb）。实验终点包括肺转移的数量和肿瘤接种小鼠的存活率。结果：我们的研究表明，与单独使用肿瘤脉冲的 DC 相比，用抗 CD3 mAb 武装肿瘤脉冲的 DC 在减少肺转移数量和存活时间方面具有更好的结果。此外，过继转移实验表明，来自 DC/R/抗 CD3 mAb 处理的小鼠的脾细胞在减少严重联合免疫缺陷 (SCID) 米色小鼠肾癌肺转移方面优于来自 DC/R 处理的小鼠的脾细胞。结论：我们的数据表明，用肿瘤脉冲的 DC 的治疗效果 可以通过使用抗 CD3 单克隆抗体来增强细胞。目前临床试验中正在进行的基于 DC 的治疗方案可能会通过为此类细胞配备抗 CD3 mAb 来得到改进。
Background:Dendritic cells (DCs) pulsed with tumor cells or peptides are effective antitumor agents in a number of tumor models. In light of our earlier demonstration that T-cell signaling via the CD3 proteins induces cytolytic activity and constrains tumor progression, we equipped DCs pulsed with tumor cells with anti-CD3 mAbs and tested their antitumor efficacy in a murine renal cell cancer pulmonary metastasis model.Methods:We investigated the antitumor efficacy of DCs pulsed with whole irradiated tumor cells (DC/R) or DCs pulsed with irradiated tumor cells and armed with anti-CD3 mAbs (DC/R/anti-CD3 mAbs). Experimental end points included the number of pulmonary metastases and survival of tumor-inoculated mice.Results:Our studies demonstrate that arming tumor-pulsed DCs with anti-CD3 mAbs results in a superior outcome compared to that from tumor-pulsed DCs alone in terms of reduction in the number of pulmonary metastases and survival times. Furthermore, adoptive transfer experiments revealed that the splenocytes from DC/R/anti-CD3 mAbs-treated mice are superior to splenocytes from DC/R-treated mice in reducing renal cancer pulmonary metastases in severe combined immunodeficient (SCID) beige mice.Conclusion:Our data suggest that the therapeutic efficacy of DCs pulsed with tumor cells can be augmented by arming them with anti-CD3 mAbs. DC-based treatment regimens that currently are being pursued in clinical trials might be improved by equipping such cells with anti-CD3 mAbs.