IP-10 enhances the amplification capacity and antitumor activity of CAR-T cells in vitro and could influence positive outcomes in MM patients treated with CAR-T cell therapy
IP-10 enhances the amplification capacity and antitumor activity of CAR-T cells in vitro and could influence positive outcomes in MM patients treated with CAR-T cell therapy
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IP-10 增强 CAR-T 细胞的体外扩增能力和抗肿瘤活性，并可能影响接受 CAR-T 细胞治疗的 MM 患者的积极结果
DOI：
10.1016/j.intimp.2022.109253
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发表时间：
2022
影响因子：
5.6
通讯作者：
Aichun Liu
中科院分区：
文献类型：
--
作者：
Tianjiao Liu;Xiaoliu Long;Yuanyuan Zhang;Jin Jin;Liting Chen;Aichun Liu
嵌合抗原受体（CAR）T细胞疗法在血液恶性肿瘤中显示出令人印象深刻的结果。然而，许多患者由于扩张和转运不良而经历有限的反应和肿瘤复发。第四代汽车解决了CAR-T细胞疗法的一些局限性，并且细胞因子由于其在T细胞发育和稳态中的重要性而经常被包括在第四代汽车中。然而，仍然需要新的探索，以提供更多可取的可能性。在这里，我们首先分析了18例接受BCMA-CAR-T细胞免疫治疗的多发性骨髓瘤（MM）患者的临床数据。数据显示，IP-10的基础血清水平与CAR-T细胞治疗后一年的患者结局相关，较高的IP-10基础血清水平与无进展生存期（PFS）呈正相关。接下来，我们使用基于流式细胞术的测定、酶联免疫吸附测定和细胞毒性测定进行体外实验。数据验证了IP-10可以有效刺激CD 8 + CAR-T细胞的趋化性。此外，在补充IP-10的培养基中培养的CAR-T细胞具有更大的增殖能力和更强大的以较低的效应物：靶比杀死肿瘤细胞的能力。因此，我们的研究结果表明，IP-10可以增强CAR-T细胞的功能，这对改善CAR-T细胞免疫治疗血液系统恶性肿瘤具有重要意义。
Chimeric antigen receptor (CAR) T-cell therapy has shown impressive outcomes in haematologic malignancies. However, many patients experience a limited response and tumour relapse because of poor expansion and transport. Fourth-generation CARs address some of the limitations of CAR-T cell therapy, and cytokines are frequently included in fourth-generation CARs due to their importance in T cell development and homeostasis. However, new explorations are still needed to provide more desirable possibilities. Here, we first analysed clinical data from 18 patients with multiple myeloma (MM) who received immunotherapy with BCMA-CAR-T cells. The data showed that the basal serum level of IP-10 was correlated with patient outcomes one year after CAR-T cell therapy and that a higher basal serum level of IP-10 was positively associated with progression-free survival (PFS). Next, we performed in vitro experiments using flow cytometry-based assays, enzyme-linked immunosorbent assays, and cytotoxicity assays. The data verified that IP-10 can effectively stimulate the chemotaxis of CD8+ CAR-T cells. In addition, CAR-T cells cultured in IP-10-supplemented medium had a greater proliferation ability and a more powerful ability to kill tumour cells at a lower effector: target ratio. Thus, our findings demonstrate that IP-10 can enhance the function of CAR-T cells, which has important implications for improving CAR-T cell immunotherapy for haematologic malignancies.