肿瘤细胞治疗研究
英文原题：Novel Local "Off-the-Shelf" Immunotherapy for the Treatment of Myeloma Bone Disease.
这些结果提示，FINM有潜力作为一种异体“现货型”方法，改善MBD患者的结局。
多发性骨髓瘤骨病（MBD）是多发性骨髓瘤（MM）——第二常见的血液系统恶性肿瘤——的主要并发症之一。其特征是由于增殖的MM细胞的局部作用而形成骨病变，迄今为止，尚未开发出有效的治疗方法。在本研究中，我们提出了一种新的MBD局部治疗方法，即在纤维蛋白支架内联合使用NK 细胞（NKs）和间充质干细胞（MSCs），统称为FINM。NKs和MSCs独特的生物学特性，加上可注射的生物相容性纤维蛋白，使得我们能够获得一种高效的“现成”即用型复合材料，用于MBD的局部治疗。我们的体外分析表明，FINM中的NKs对MM细胞系和原代细胞发挥强大的抗肿瘤活性，并能够在体外3D MBD模型中抑制破骨细胞活性（约60%）。此外，在MSCs存在的情况下，NKs解冻后的细胞毒性活性显著增强（约75%），这规避了NKs解冻后细胞毒性下降的问题，而这是NKs冷冻保存中一个众所周知的问题。为了减少肿瘤逃逸，我们将FINM与其他治疗药物（硼替佐米（BZ）和肿瘤坏死因子相关凋亡诱导配体（TRAIL））联合使用，在体外观察到明显的治疗协同效应。最后，在MM小鼠模型中评估了FINM联合BZ和TRAIL的治疗效果，与未经治疗的对照组相比，肿瘤缩小了16倍。这些结果表明，FINM有潜力作为一种同种异体“现成”方法，以改善MBD患者的预后。
Myeloma bone disease (MBD) is one of the major complications in multiple myeloma (MM)-the second most frequent hematologic malignancy. It is characterized by the formation of bone lesions due to the local action of proliferating MM cells, and to date, no effective therapy has been developed. In this study, we propose a novel approach for the local treatment of MBD with a combination of natural killer cells (NKs) and mesenchymal stem cells (MSCs) within a fibrin scaffold, altogether known as FINM. The unique biological properties of the NKs and MSCs, joined to the injectable biocompatible fibrin, permitted to obtain an efficient "off-the-shelf" ready-to-use composite for the local treatment of MBD. Our in vitro analyses demonstrate that NKs within FINM exert a robust anti-tumor activity against MM cell lines and primary cells, with the capacity to suppress osteoclast activity (~60%) within in vitro 3D model of MBD. Furthermore, NKs' post-thawing cytotoxic activity is significantly enhanced (~75%) in the presence of MSCs, which circumvents the decrease of NKs cytotoxicity after thawing, a well-known issue in the cryopreservation of NKs. To reduce the tumor escape, we combined FINM with other therapeutic agents (bortezomib (BZ), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)), observing a clear therapeutic synergistic effect in vitro. Finally, the therapeutic efficacy of FINM in combination with BZ and TRAIL was assessed in a mouse model of MM, achieving 16-fold smaller tumors compared to the control group without treatment. These results suggest the potential of FINM to serve as an allogeneic "off-the-shelf" approach to improve the outcomes of patients suffering from MBD.
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