Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C
作者机构:Department of Clinical ImmunologyXijing HospitalDepartment of Cell BiologyNational Translational Science Center for Molecular MedicineFourth Military Medical UniversityXi'an710032China Beijing Tricision Biotherapeutics Inc.Beijing100176China Department of NeurosurgeryXijing HospitalFourth Military Medical UniversityXi'an710032China Zhuhai Tricision Biotherapuetics Inc.ZhuhaiGuangdong519040China Department of Pharmacology and Molecular SciencesJohns Hopkins University School of MedicineBaltimoreMD21205USA
出 版 物:《Journal of Pharmaceutical Analysis》 (药物分析学报(英文版))
年 卷 期:2023年第13卷第6期
页 面:616-624页
核心收录:
学科分类:1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
主 题:Glioblastoma multiforme DC vaccine Tumor-associated antigens Neoantigens
摘 要:Glioblastoma(GBM)is a lethal cancer with limited therapeutic *** cell(DC)-based cancer vaccines provide a promising approach for GBM *** studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor ***,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 *** 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 ***,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 *** treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC *** patient also received 28 doses of cyclophosphamide for depletion of regulatory T *** immunotherapy-related adverse events were observed during the *** antitumor CD4t and CD8t T-cell responses were *** patient remains free of disease *** is the first case report on the combination of the above three agents to treat glioblastoma *** 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.