免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Immunological responses to adjuvant vaccination with combined CD1c(+) myeloid and plasmacytoid dendritic cells in stage III melanoma patients.
Immunological responses to adjuvant vaccination with combined CD1c(+) myeloid and plasmacytoid dendritic cells in stage III melanoma patients.
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我们评估了淋巴结受累(III期)黑色素瘤患者对使用天然存在的树突状细胞(nDCs)亚群进行辅助性树突状细胞疫苗接种的免疫学应答。15例完全切除的III期黑色素瘤患者被随机分配接受CD1c+髓系树突状细胞(cDC2s)、浆细胞样树突状细胞(pDCs)或两者联合的辅助性树突状细胞疫苗接种。免疫学应答是主要终点,次要终点包括安全性和生存。在80%的患者中,在皮肤试验来源的T细胞中检测到抗原特异性CD8+T细胞,在55%的患者中,在外周血中可检测到抗原特异性CD8+T细胞。在64%的患者皮肤试验中发现有功能的产生干扰素-γ的T细胞。所有患者均能生产符合放行标准的nDC疫苗。疫苗接种仅诱导1-2级不良事件,主要包括疲劳。总之,使用cDC2s和/或pDCs进行辅助性树突状细胞疫苗接种是可行的、安全的,并在大多数III期黑色素瘤患者中诱导了免疫学应答。
We evaluated the immunological responses of lymph-node involved (stage III) melanoma patients to adjuvant dendritic cell vaccination with subsets of naturally occurring dendritic cells (nDCs). Fifteen patients with completely resected stage III melanoma were randomized to receive adjuvant dendritic cell vaccination with CD1c + myeloid dendritic cells (cDC2s), plasmacytoid dendritic cells (pDCs) or the combination. Immunological response was the primary endpoint and secondary endpoints included safety and survival.
In 80% of the patients, antigen-specific CD8 + T cells were detected in skin test-derived T cells and in 55% of patients, antigen-specific CD8 + T cells were detectable in peripheral blood. Functional interferon-γ-producing T cells were found in the skin test of 64% of the patients. Production of nDC vaccines meeting release criteria was feasible for all patients. Vaccination only induced grade 1-2 adverse events, mainly consisting of fatigue.
In conclusion, adjuvant dendritic cell vaccination with cDC2s and/or pDCs is feasible, safe and induced immunological responses in the majority of stage III melanoma patients.
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