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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 *** 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,inc.uding 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.

关键词： Glioblastoma multiforme DC vaccine Tumor-associated antigens Neoantigens

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Sintilimab (anti-PD-1 antibody) combined with high-dose methotrexate, temozolomide, and rituximab (anti-CD20 antibody) in primary central nervous system lymphoma: a phase 2 study

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Signal Transduction and Targeted Therapy 2024年第10期9卷 4554-4563页

作者： Zhiyong Zeng Apeng Yang Jingke Yang Sheng Zhang Zhen Xing Xingfu Wang Wenzhong Mei Changzhen Jiang Junfang Lin Xiyue Wu Yihui Xue Zanyi Wu Lianghong Yu Dengliang Wang Jianwu Chen Shufa Zheng Qiaoxian Lin Qingjiao Chen Jinfeng Dong Xiaoqiang Zheng Jizhen Wang Jinlong Huang Zhenying Chen Ping Chen Meihong Zheng Xiaofang Zhou Youwen He Yuanxiang Lin Junmin Chen Department of Hematology the First Affiliated Hospital of Fujian Medical UniversityFuzhouChina Department of Hematology National Regional Medical CenterBinhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhouChina Fujian Lymphoma and Multiple Myeloma Working Group FuzhouChina Parexel International DurhamNorth CarolinaUSA Department of Pathology the First Affiliated Hospital of Fujian Medical UniversityFuzhouChina Department of Imaging the First Affiliated Hospital of Fujian Medical UniversityFuzhouChina Department of Neurosurgery the First Affiliated Hospital of Fujian Medical UniversityFuzhouChina Department of Nuclear Medicine the First Affiliated Hospital of Fujian Medical UniversityFuzhouChina beijing tricision biotherapeutics inc. BeijingChina

Primary central nervous system lymphoma(PCNSL)is a rare and frequently fatal lymphoma *** programmed death-1(PD-1)pathway has emerged as a potential therapeutic target,but the effectiveness of PD-1 antibody sintilimab in combination with immunochemotherapy as a frontline treatment for PCNSL remains to be *** this phase 2 trial(ChiCTR1900027433)with a safety run-in,we inc.uded patients aged 18–70 with newly diagnosed *** underwent six 21-day cycles of a SMTR regimen,which inc.udes sintilimab(200 mg,Day 0),rituximab(375 mg/m2,Day 0),methotrexate(3.0 g/m2,Day 1 or 1.0 g/m2 for patients aged≥65 years),and temozolomide(150 mg/m2/d,Days 1–5).Among 27 evaluable patients,the overall response rate(ORR)was 96.3%(95%confidence interval:81–99.9%),with 25 complete *** a median follow-up of 24.4 months,the medians for duration of response,progression-free survival(PFS),and overall survival were not *** most common grade 3–4 treatment-related toxicities were inc.eased levels of alanine aminotransferase(17.9%)and aspartate aminotransferase(14.3%).Additionally,baseline levels of interferon-αand the IL10/IL6 ratio in cerebrospinal fluid emerged as potential predictors of PFS,achieving areas under the curve of 0.88 and 0.84,respectively,at 2 ***-exome sequencing revealed a higher prevalence of RTK-RAS and PI3K pathway mutations in the durable clinical benefit group,while a greater frequency of Notch and Hippo pathway mutations in the no durable benefit *** findings suggest the SMTR regimen is highly efficacious and tolerable for newly diagnosed PCNSL,warranting further investigation.

关键词： methotrexate lymphoma system

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