Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.
Am J Hematol. 2019 May;94(S1):S28-S33. doi: 10.1002/ajh.25428. Epub 2019 Feb 25.
Multiple myeloma (MM) is a malignant plasma cell disorder that remains incurable for most patients despite significant improvements achieved with modern therapy. Tumor evasion is a key process in the pathogenesis of MM and a compromised immune system is associated with more aggressive forms of the disease. In contrast, the emergence of myeloma-specific immune responses after both autologous and allogeneic stem cell transplantation is associated with better prognosis. Adoptive T cell therapies may improve specific anti-myeloma immunity resulting in long-lasting remissions. CAR T cell therapies for MM are at an early stage of clinical development. To date, anti-BCMA CAR T cells have shown the greatest results in early-phase clinical trials. Toxicities have included cytokine release syndrome (CRS) and neurotoxicity. Current areas of research in CAR T cell therapies include the use of gene-editing to enhance their effectiveness and safety, the integration of CAR T cells with other therapies (immunomodulatory drugs, checkpoint inhibitors) and CAR T cells to target multiple antigens.
多发性骨髓瘤（MM）是一种恶性浆细胞疾病，尽管现代疗法取得了显著进展，但大多数患者仍无法治愈。肿瘤逃逸是 MM 发病机制中的一个关键过程，免疫系统受损与疾病更具侵袭性的形式相关。相比之下，自体和异基因干细胞移植后出现的骨髓瘤特异性免疫反应与更好的预后相关。过继性 T 细胞疗法可能会改善特定的抗骨髓瘤免疫，从而实现持久缓解。嵌合抗原受体 T 细胞（CAR T）疗法在 MM 的临床开发中处于早期阶段。迄今为止，抗 BCMA CAR T 细胞在早期临床试验中显示出最大的疗效。毒性包括细胞因子释放综合征（CRS）和神经毒性。CAR T 细胞疗法的当前研究领域包括使用基因编辑来提高其有效性和安全性，将 CAR T 细胞与其他疗法（免疫调节药物、检查点抑制剂）和 CAR T 细胞结合以靶向多种抗原。
