细胞及疫苗免疫疗法在多发性骨髓瘤中的研究进展

Progress of cellular and vaccine immunotherapy in multiple myeloma

异基因造血干细胞移植和供者淋巴细胞输注能诱导多发性骨髓瘤（MM）患者的移植物抗骨髓瘤免疫效应，从而使患者获得长期生存，但其疗效的局限性和相关毒性限制了其在临床上的广泛应用。因此，目前正在寻求更有效的细胞免疫疗法和疫苗疗法，以诱导更特异、更稳定和更有效的抗骨髓瘤免疫应答反应，同时降低治疗相关的风险。随着分子生物学、基础免疫学和应用免疫学的发展，催生了一系列极具前景的MM治疗方法，如抗原特异性的嵌合受体和骨髓瘤特异性表位的靶向T细胞受体等修饰T细胞、疫苗致敏并体外扩增自体T细胞、扩增骨髓浸润的淋巴细胞及浆细胞、树突状细胞融合疫苗等。这些新兴的治疗方案与免疫调节制剂、程序性死亡受体1（PD-1）T细胞调节通路抑制剂结合，有望改善MM患者的治疗效果。介绍第58届美国血液学会（ASH）年会报道的关于细胞和疫苗免疫疗法在MM治疗中的相关信息，并探讨了将这些疗法与现有的治疗方案整合治疗MM的可行性。

Allogeneic hematopoietic stem cell transplantation and donor lymphocyte infusion for multiple myeloma （MM） can induce graft-versus-myeloma immunity and long-term survival, but limited efficacy and associated toxicities have prevented its widespread application. Cellular immunotherapies and vaccines are explored to induce more specific, reliable, and potent antimyeloma immune responses with less treatment-related risk. Advances in molecular biology, basic and applied immunology, have led to several promising approaches such as genetically engineered T cells with chimeric antigen receptors and T-cell receptors targeting myeloma-specific epitopes, vaccine primed ex vivo expanded autologous T cells, expanded marrow-infiltrating lymphocytes, and plasma cell/dendritic cell fusion vaccines. The combination of these emerging therapies to immunomodulatory drugs and inhibitors of programmed death-1 T-cell regulatory pathways could improve the outcome for MM patients. This article reviews the latest progress of cellular and vaccine immunotherapy for MM at the 58th American Society of Hematology （ASH） Annual Meeting, and discusses how these therapies might integrate and synergize with existing treatment paradigms.