CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Human T cells loaded with superparamagnetic iron oxide nanoparticles retain antigen-specific TCR functionality.
Human T cells loaded with superparamagnetic iron oxide nanoparticles retain antigen-specific TCR functionality.
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我们证明了 T 细胞负载 SPION 不影响细胞力学或内源性或外源性 TCR 的功能，这为未来利用 SPION 在实体瘤中磁性富集 T 细胞的方法提供了可能。
癌症免疫治疗是一个新兴领域，具有改善长期生存的潜力。迄今为止，肿瘤特异性T细胞的过继转移是血液系统肿瘤如淋巴瘤、白血病或骨髓瘤的有效治疗选择。然而，在实体瘤中，由于免疫抑制微环境、靶向/脱靶毒性、从血管外渗受限或T细胞向肿瘤区域转运无效，治疗效果较低。超顺磁性氧化铁纳米颗粒（SPIONs）可使细胞具有磁性可控性，以实现位点特异性富集。
在本研究中，我们探讨了SPION负载对用于磁靶向过继性T细胞疗法的原代人T细胞的影响。为此，我们分析了通过针对黑色素瘤抗原MelanA的外源性T细胞受体（TCR）或针对巨细胞病毒抗原pp65的内源性TCR刺激后的细胞力学和T细胞反应，并将其与未接受SPION的T细胞进行了比较。
SPION负载对人T细胞的细胞力学没有影响，因此保留了其在外界压力下变形的能力。此外，SPION负载不损害T细胞增殖、活化标志物表达、细胞因子分泌以及在TCR介导的抗原特异性活化后的肿瘤细胞杀伤能力。
Immunotherapy of cancer is an emerging field with the potential to improve long-term survival. Thus far, adoptive transfer of tumor-specific T cells represents an effective treatment option for tumors of the hematological system such as lymphoma, leukemia or myeloma. However, in solid tumors, treatment efficacy is low owing to the immunosuppressive microenvironment, on-target/off-tumor toxicity, limited extravasation out of the blood vessel, or ineffective trafficking of T cells into the tumor region. Superparamagnetic iron oxide nanoparticles (SPIONs) can make cells magnetically controllable for the site-specific enrichment.
In this study, we investigated the influence of SPION-loading on primary human T cells for the magnetically targeted adoptive T cell therapy. For this, we analyzed cellular mechanics and the T cell response after stimulation via an exogenous T cell receptor (TCR) specific for the melanoma antigen MelanA or the endogenous TCR specific for the cytomegalovirus antigen pp65 and compared them to T cells that had not received SPIONs.
SPION-loading of human T cells showed no influence on cellular mechanics, therefore retaining their ability to deform to external pressure. Additionally, SPION-loading did not impair the T cell proliferation, expression of activation markers, cytokine secretion, and tumor cell killing after antigen-specific activation mediated by the TCR.
In summary, we demonstrated that SPION-loading of T cells did not affect cellular mechanics or the functionality of the endogenous or an exogenous TCR, which allows future approaches using SPIONs for the magnetically enrichment of T cells in solid tumors.
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →
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