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

Journal of Pharmaceutical Analysis 2023年第6期13卷 616-624页

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 Department of Clinical Immunology Xijing HospitalDepartment of Cell BiologyNational Translational Science Center for Molecular MedicineFourth Military Medical UniversityXi'an710032China Beijing Tricision Biotherapeutics Inc. Beijing100176China Department of Neurosurgery Xijing HospitalFourth Military Medical UniversityXi'an710032China Zhuhai Tricision Biotherapuetics Inc. ZhuhaiGuangdong519040China Department of Pharmacology and Molecular Sciences Johns Hopkins University School of MedicineBaltimoreMD21205USA

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

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mRNA cancer vaccines:Advances,trends and challenges

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Acta Pharmaceutica Sinica B 2022年第7期12卷 2969-2989页

作者： Qing He Hua Gao Dejiang Tan Heng Zhang Jun-zhi Wang National Institutes for Food and Drug Control State Key Laboratory for Evaluation and Standardization of Innovative Vaccines and Biotechnology ProductsBeijing 102629China

Patients exhibit good tolerance to messenger ribonucleic acid(m RNA)vaccines,and the choice of encoded molecules is flexible and diverse.These vaccines can be engineered to express full-length antigens containing multiple epitopes without major histocompatibility complex(MHC)restriction,are relatively easy to control and can be rapidly mass produced.In 2021,the U.S.Food and Drug Administration(FDA)approved the first m RNA-based coronavirus disease 2019(COVID-19)vaccine produced by Pfizer and Bio NTech,which has generated enthusiasm for m RNA vaccine research and development.Based on the above characteristics and the development of m RNA vaccines,m RNA cancer vaccines have become a research hotspot and have undergone rapid development,especially in the last five years.This review analyzes the advances in m RNA cancer vaccines from various perspectives,including the selection and expression of antigens/targets,the application of vectors and adjuvants,different administration routes,and preclinical evaluation,to reflect the trends and challenges associated with these vaccines.

关键词： mRNA Cancer vaccine tumor-associated antigens Neoantigens mRNA delivery vectors Adjuvants Administration routes

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An in situ nanoparticle recombinant strategy for the enhancement of photothermal therapy

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Chinese Chemical Letters 2022年第1期33卷 328-333页

作者： Xinxin Liu Cuixia Zheng Yueyue Kong Hao Wang Lei Wang Luoyang Central Hospital Affiliated to Zhengzhou University Luoyang 471009China School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China Key Laboratory of Advanced Drug Preparation Technologies Ministry of EducationSchool of Pharmaceutical SciencesZhengzhou UniversityZhengzhou 450001China Henan Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases Zhengzhou UniversityZhengzhou 450001China tumor Immunity and Biomaterials Advanced Medical Center Zhengzhou UniversityLuoyang 471009China

Photothermal therapy(PTT)-induced immune response has attracted much attention,however,which cannot work at full capacity.In this study,the simvastatin(SV)adjuvant is loaded into gold nanocages(AuNCs)to develop a simple drug delivery system,which can efficiently utilize the tumor-associated antigens(TAAs)for improving immune responses.AuNCs/SV-mediated PTT treatment enhances tumor cells damage and promotes the release of TAAs which are immediately captured by Au NCs/SV to form AuNCs/SV/TAAs recombinant nanoparticle.Impressively,AuNCs/SV/TAAs can accumulate in lymph nodes effectively due to the suitable size of~55 nm and hyperthermia-induced vasodilative effect.And the codelivery of antigen and adjuvant is beneficial to stimulating the maturation of dendritic cells for further activating T cells.In a word,the recombinant strategy could make full use of TAAs to produce an individual powerful immunotherapy.

关键词： Photothermal therapy tumor-associated antigens Recombinant nanoparticle T cells activation Individual immunotherapy

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