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

作　　者：Ping Zhu Shi-You Li Jin Ding Zhou Fei Sheng-Nan Sun Zhao-Hui Zheng Ding Wei Jun Jiang Jin-Lin Miao San-Zhong Li Xing Luo Kui Zhang Bin Wang Kun Zhang Su Pu Qian-Ting Wang Xin-Yue Zhang Gao-Liu Wen Jun OLiu John Thomas August Huijie Bian Zhi-Nan Chen You-Wen He 

机构地区：[1]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 [2]Beijing Tricision Biotherapeutics Inc.,Beijing,100176,China [3]Department of Neurosurgery,Xijing Hospital,Fourth Military Medical University,Xi'an,710032,China [4]Zhuhai Tricision Biotherapuetics Inc.,Zhuhai,Guangdong,519040,China [5]Department of Pharmacology and Molecular Sciences,Johns Hopkins University School of Medicine,Baltimore,MD,21205,USA

出　　处：《Journal of Pharmaceutical Analysis》2023年第6期616-624,共9页药物分析学报（英文版）

基　　金：supported by Natural Science Foundation of Shaanxi Province(Grant No.:2019ZY-CXPT-03-01)to Ping Zhu and Key Research and Development Program of Shaanxi Province(Grant No.:2020ZDLSF03-02)to Zhi-Nan Chen and Huijie Bian as well as Tricision Biotherapeutics Inc.

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 immunotherapeutic 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-TAAs 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 histocompatibility 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 CD4t and CD8t 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.

关 键 词：Glioblastoma multiforme DC vaccine Tumor-associated antigens Neoantigens 

分 类 号：R965[医药卫生—药理学]