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

作者：Ping Zhu, Shiyou Li, Jin Ding, Zhou Fei, Shengnan Sun, Zhaohui Zheng, Ding Wei, Jun Jiang, Jinlin Miao, Sanzhong Li, Xing Luo, Kui Zhang, Bin Wang, Kun Zhang, Pu Su, Qianting Wang, Xin-Yue Zhang, Gao-Liu Wen, Jun O. Liu, John Thomas August, Huijie Bian, Zhi‐Nan Chen, You‐Wen He · 发表于：Journal of Pharmaceutical Analysis · 年份：2023 · DOI：10.1016/j.jpha.2023.04.012 · 被引用次数：56 · 研究领域：Immunotherapy and Immune Responses、Glioma Diagnosis and Treatment、Cancer Immunotherapy and Biomarkers

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 CD4+ and CD8+ T-cell responses were detected. The patient remains free of disease progression ...