肿瘤细胞治疗研究
英文原题：Langerhans dendritic cell vaccine bearing mRNA-encoded tumor antigens induces antimyeloma immunity after autotransplant.
ASCT后3个月，所有患者开始接受来那度胺维持治疗。
移植后针对残留病灶的疫苗接种是一种免疫治疗策略，旨在改善抗原特异性免疫反应并延长多发性骨髓瘤（MM）自体干细胞移植（ASCT）后的无病生存期。我们开展了一项1期疫苗试验，以确定在MM患者ASCT后，电穿孔导入CT7、MAGE-A3和Wilms瘤1（WT1）信使RNA（mRNA）的自体朗格汉斯型树突状细胞（LCs）的安全性、毒性和免疫原性。10例患者在ASCT后第12、30和90天分别接受了1次初始免疫加2次加强免疫。疫苗含有9 × 106个mRNA电穿孔LCs。另有10例患者未接受LC疫苗，但接受了其他方面完全相同的ASCT和支持治疗。ASCT后3个月时，所有患者开始来那度胺维持治疗。接种疫苗的患者在加强免疫后出现轻度局部迟发型超敏反应，但无毒性超过1级。疫苗接种后1个月和3个月时，抗原特异性CD4和CD8 T细胞分泌促炎细胞因子（干扰素-γ、白细胞介素-2和肿瘤坏死因子-α）较疫苗前水平增加，并且上调了细胞毒性标志物CD107a。CD4和CD8 T细胞库分析显示，疫苗队列中克隆扩增增加的趋势，这在CD4区室中更为明显。尽管该研究未以评估临床疗效为效能目标，但治疗反应倾向于疫苗组。在MM患者ASCT后植入时启动的携带三重抗原的mRNA电穿孔自体LC疫苗接种，联合标准来那度胺维持治疗，是安全的，并可诱导抗原特异性免疫反应性。该试验在www.clinicaltrials.gov注册，编号为#NCT01995708。
Posttransplant vaccination targeting residual disease is an immunotherapeutic strategy to improve antigen-specific immune responses and prolong disease-free survival after autologous stem cell transplantation (ASCT) for multiple myeloma (MM). We conducted a phase 1 vaccine trial to determine the safety, toxicity, and immunogenicity of autologous Langerhans-type dendritic cells (LCs) electroporated with CT7, MAGE-A3, and Wilms tumor 1 (WT1) messenger RNA (mRNA), after ASCT for MM. Ten patients received a priming immunization plus 2 boosters at 12, 30, and 90 days, respectively, after ASCT. Vaccines contained 9 × 106 mRNA-electroporated LCs. Ten additional patients did not receive LC vaccines but otherwise underwent identical ASCT and supportive care. At 3 months after ASCT, all patients started lenalidomide maintenance therapy. Vaccinated patients developed mild local delayed-type hypersensitivity reactions after booster vaccines, but no toxicities exceeded grade 1. At 1 and 3 months after vaccines, antigen-specific CD4 and CD8 T cells increased secretion of proinflammatory cytokines (interferon-γ, interleukin-2, and tumor necrosis factor-α) above prevaccine levels, and also upregulated the cytotoxicity marker CD107a. CD4 and CD8 T-cell repertoire analysis showed a trend for increased clonal expansion in the vaccine cohort, which was more pronounced in the CD4 compartment. Although not powered to assess clinical efficacy, treatment responses favored the vaccine arm. Triple antigen-bearing mRNA-electroporated autologous LC vaccination initiated at engraftment after ASCT, in conjunction with standard lenalidomide maintenance therapy for MM, is safe and induces antigen-specific immune reactivity. This trial was registered at www.clinicaltrials.gov as #NCT01995708.
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