Vasileiou Spyridoula, Baltadakis Ioannis, Delimpasi Sosanna, Karatza Maria-Helena, Liapis Konstantinos, Garofalaki Maria, Tziotziou Eirini, Poulopoulou Zoe, Karakasis Dimitri, Harhalakis Nicholas
Department of Haematology, Bone Marrow Transplantation Unit, Evangelismos Hospital, Athens, Greece.
J Immunother. 2017 Sep;40(7):253-264. doi: 10.1097/CJI.0000000000000182.
The introduction of novel agents has significantly expanded treatment options for multiple myeloma (MM), albeit long-term disease control cannot be achieved in the majority of patients. Vaccination with MM antigen-loaded dendritic cells (DCs) represents an alternative strategy that is currently being explored. The aim of this study was to assess the immunogenic potential of ex vivo-generated monocyte-derived DCs (moDCs), following stimulation with the whole-antigen array of autologous myeloma cells (AMC). MoDCs were loaded with antigens of myeloma cells by 2 different methods: phagocytosis of apoptotic bodies from γ-irradiated AMC, or transfection with AMC total RNA by square-wave electroporation. Twenty patients with MM were enrolled in the study. Following stimulation and maturation, moDCs were tested for their capacity to induce T-helper 1 and cytotoxic T lymphocyte responses in vitro. Both strategies were effective in the induction of myeloma-specific cytotoxic T lymphocyte and T-helper 1 cells, as demonstrated by cytotoxicity and ELISpot assays. On the whole, T-cell responses were observed in 18 cases by either method of DC pulsing. We conclude that both whole-tumor antigen approaches are efficient in priming autologous antimyeloma T-cell responses and warrant further study aiming at the development of individualized DC vaccines for MM patients.
新型药物的引入显著扩展了多发性骨髓瘤(MM)的治疗选择,尽管大多数患者无法实现长期疾病控制。用负载MM抗原的树突状细胞(DC)进行疫苗接种是目前正在探索的一种替代策略。本研究的目的是评估用自体骨髓瘤细胞(AMC)的全抗原阵列刺激后,体外生成的单核细胞来源的DC(moDC)的免疫原性潜力。通过两种不同方法用骨髓瘤细胞抗原负载moDC:吞噬来自γ射线照射的AMC的凋亡小体,或通过方波电穿孔用AMC总RNA转染。20例MM患者纳入本研究。刺激和成熟后,检测moDC在体外诱导辅助性T细胞1和细胞毒性T淋巴细胞反应的能力。细胞毒性和ELISpot分析表明,两种策略在诱导骨髓瘤特异性细胞毒性T淋巴细胞和辅助性T细胞1方面均有效。总体而言,通过任何一种DC脉冲方法在18例中观察到T细胞反应。我们得出结论,两种全肿瘤抗原方法在引发自体抗骨髓瘤T细胞反应方面均有效,值得进一步研究以开发针对MM患者的个性化DC疫苗。