CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Generation and quality control of mature monocyte-derived dendritic cells for immunotherapy.
Generation and quality control of mature monocyte-derived dendritic cells for immunotherapy.
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树突状细胞疫苗是一种主动免疫治疗形式,旨在利用DC在启动T细胞应答中的关键作用。目前已针对多种肿瘤开展了大量疫苗接种试验,包括胶质母细胞瘤——成人中最常见且最具侵袭性的恶性脑肿瘤。这些试验已证明其可行性和安全性,并提示可改善生存期,与抗肿瘤免疫的诱导相关。在此,我们详细描述一种大规模两步方案,用于连续GMP合规地生成未成熟和成熟树突状细胞,可获得高度均一的CD83+成熟DC群体,高密度表达CD40、CD80、CD86和HLA-DR,缺乏免疫抑制酶吲哚胺-2,3-双加氧酶的活性,可向趋化因子CCL19迁移,并表现出强效的T细胞刺激活性。这些细胞负载自体肿瘤裂解物后,目前正在胶质母细胞瘤患者中接受一项II期对照随机临床试验(GlioVax)的评估。
Dendritic cell vaccination is a form of active immunotherapy that aims to exploit the crucial role of DC in the initiation of T-cell responses. Numerous vaccination trials have been conducted targeting various tumor entities, including glioblastoma, the most frequent and aggressive malignant brain tumor in adults. They have demonstrated feasibility and safety and suggest improved survival, associated with induction of anti-tumoral immunity.
Here, we describe in detail a large-scale 2-step protocol for successive GMP-compliant generation of immature and mature dendritic cells, yielding a highly homogenous population of CD83 + mature DC expressing CD40, CD80, CD86 and HLA-DR at high density, lacking activity of the immunosuppressive enzyme indoleamine-2,3-dioxygenase, migrating towards the chemokine CCL19 and showing highly potent T-cell stimulatory activity.
Loaded with autologous tumor lysate, these cells are currently being evaluated in a phase II controlled randomized clinical trial (GlioVax) in glioblastoma patients.
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