Ex vivo expansion of non-MHC-restricted cytotoxic effector cells as adoptive immunotherapy for myeloma.
Ex vivo expansion of non-MHC-restricted cytotoxic effector cells as adoptive immunotherapy for myeloma.
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非 MHC 限制性细胞毒性效应细胞的离体扩增作为骨髓瘤的过继免疫疗法。
DOI：
10.1080/14653240600620218
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发表时间：
2006
期刊：
影响因子：
4.5
通讯作者：
Meehan,KR
中科院分区：
文献类型：
--
作者：
Wu,JY;Ernstoff,MS;Hill,JM;Cole,B;Meehan,KR
背景 PBMC 可以离体扩增为包含 T、NK 和 NKT 细胞的侵袭性细胞毒性效应细胞 (CEC)。我们鉴定了这些 CEC 的表型、细胞毒性和杀伤机制。方法将来自骨髓瘤患者的 CY 和 G-CSF 动员的 PBMC 置于 Aim-V 无血清培养基、IL-2 (50 IU/mL) 和 OKT-3 (50 ng/mL) 中。通过选择性阻断 TCR、MHC I 类或 NKG2D 受体来评估细胞毒性。结果与第 0 天（4%；P=0.012）相比，CEC 在第 7 天扩增了三倍，并积极裂解骨髓瘤细胞（41.9%）。 CD8+CD56+NKT 细胞进行了大部分裂解。 CD8+细胞在培养过程中大大增加了NKG2D的表达（P=0.005）。细胞毒性与靶标 NKG2D 配体表达相关 (P=0.0002)。阻断TCR或MHC I类不影响细胞毒性（P>0.22）。当 NKG2D 受体被阻断时，CD8+细胞介导的裂解下降 48%。第 7 天，CEC 通过 NKG2D 受体以 MHC 和非 MHC 限制的方式积极裂解骨髓瘤细胞。讨论由于肿瘤细胞上的 MHC 表达通常下调，并且 NKG2D 配体通常对恶性细胞具有特异性，因此通过不同途径杀伤的 CEC 过继转移可能会规避肿瘤抵抗机制并改善预后。
BackgroundPBMC can be expandedex vivointo aggressive cytotoxic effector cells (CEC) comprising T, NK and NKT cells. We identified the phenotype, cytotoxicity and mechanisms of killing of these CEC.MethodsCY- and G-CSF-mobilized PBMC from myeloma patients were placed in Aim-V serum-free medium, IL-2 (50 IU/mL) and OKT-3 (50 ng/mL). Cytotoxicity was evaluated by selectively blocking the TCR, MHC class I or NKG2D receptor.ResultsThe CEC expanded three-fold by day 7 and aggressively lysed myeloma cells (41.9%) compared with day 0 (4%;P=0.012). CD8+CD56+NKT cells performed the majority of lysis. The CD8+cells greatly increased NKG2D expression during culture (P=0.005). Cytotoxicity correlated with target NKG2D ligand expression (P=0.0002). Blocking the TCR or MHC class I did not affect cytotoxicity (P>0.22). CD8+cell-mediated lysis dropped 48% when the NKG2D receptor was blocked. Day 7 CEC aggressively lysed myeloma cells in an MHC- and non-MHC-restricted fashion, through the NKG2D receptor.DiscussionBecause MHC expression is often down-regulated on tumor cells and the NKG2D ligands are generally specific to malignant cells, the adoptive transfer of CEC that kill through different pathways may circumvent tumor-resistant mechanisms and improve outcomes.