Garfall A L, Vogl D T, Weiss B M, Stadtmauer E A
Multiple Myeloma Program, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Bone Marrow Transplant. 2013 Nov;48(11):1377-86. doi: 10.1038/bmt.2013.54. Epub 2013 May 6.
Allogeneic hematopoietic cell transplantation for plasma cell myeloma can lead to graft-vs-myeloma immunity and long-term survivorship, but limited efficacy and associated toxicities have prevented its widespread use. Cellular immunotherapies seek to induce more specific, reliable and potent antimyeloma immune responses with less treatment-related risk than is possible with allogeneic transplantation. Strategies under development include infusion of vaccine-primed and ex vivo expanded/costimulated autologous T cells after high-dose melphalan, genetic engineering of autologous T cells with receptors for myeloma-specific epitopes, administration of DC/plasma cell fusions and administration expanded marrow-infiltrating lymphocytes. In addition, novel immunomodulatory drugs such as inhibitors of the programmed death-1 T cell regulatory pathway may synergize with cellular immunotherapies.
异基因造血细胞移植治疗浆细胞骨髓瘤可引发移植物抗骨髓瘤免疫反应并实现长期生存,但疗效有限及相关毒性阻碍了其广泛应用。细胞免疫疗法旨在诱导更具特异性、可靠性和强效性的抗骨髓瘤免疫反应,且与异基因移植相比,治疗相关风险更低。正在研发的策略包括在大剂量美法仑治疗后输注经疫苗激发和体外扩增/共刺激的自体T细胞、对自体T细胞进行基因工程改造使其带有骨髓瘤特异性表位的受体、给予树突状细胞/浆细胞融合物以及输注扩增的骨髓浸润淋巴细胞。此外,新型免疫调节药物,如程序性死亡-1 T细胞调节途径抑制剂,可能与细胞免疫疗法产生协同作用。