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Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C

摘要Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

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作者 Ping Zhu [1] Shi-You Li [2] Jin Ding [1] Zhou Fei [3] Sheng-Nan Sun [2] Zhao-Hui Zheng [1] Ding Wei [1] Jun Jiang [4] Jin-Lin Miao [1] San-Zhong Li [3] Xing Luo [1] Kui Zhang [1] Bin Wang [1] Kun Zhang [1] Su Pu [2] Qian-Ting Wang [2] Xin-Yue Zhang [4] Gao-Liu Wen [4] Jun O.Liu [5] John Thomas August [5] Huijie Bian [1] Zhi-Nan Chen [1] You-Wen He [2] 学术成果认领
作者单位 Department of Clinical Immunology,Xijing Hospital,Department of Cell Biology,National Translational Science Center for Molecular Medicine,Fourth Military Medical University,Xi'an,710032,China [1] Beijing Tricision Biotherapeutics Inc.,Beijing,100176,China [2] Department of Neurosurgery,Xijing Hospital,Fourth Military Medical University,Xi'an,710032,China [3] Zhuhai Tricision Biotherapuetics Inc.,Zhuhai,Guangdong,519040,China [4] Department of Pharmacology and Molecular Sciences,Johns Hopkins University School of Medicine,Baltimore,MD,21205,USA [5]
栏目名称
DOI 10.1016/j.jpha.2023.04.012
发布时间 2023-08-07(万方平台首次上网日期,不代表论文的发表时间)
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药物分析学报(英文版)

药物分析学报(英文版)

2023年13卷6期

616-624页

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