帕博利珠单抗联合二甲双胍治疗转移性头颈部癌的 II 期可行性研究
A Phase II Feasibility Study Combining Pembrolizumab and Metformin in Patients with Metastatic Head and Neck Cancer.
二甲双胍联合帕博利珠单抗耐受性良好,仅出现轻度胃肠道不良事件,并展现出有前景的活性,值得在随机试验中进一步研究。
英文原题:A photodynamically sensitized dendritic cell vaccine that promotes the anti-tumor effects of anti-PD-L1 monoclonal antibody in a murine model of head and neck squamous cell carcinoma.
PDT-DC疫苗增强了PD-L1抗体的治疗效果,这可能为HNSCC免疫治疗提供一种新方法。
免疫检查点抑制剂是抗击包括头颈部鳞状细胞癌(HNSCC)在内的多种癌症的有前景的工具。然而,相当一部分HNSCC患者对PD-L1抗体无应答。在此,我们描述了一种光动力治疗(PDT)方法,以增强抗PD-L1抗体的抗肿瘤效果。
PDT的光毒性通过荧光显微镜、Cell Counting Kit-8 (CCK-8)、酶联免疫吸附试验(ELISA)和流式细胞术分析得到证实。通过流式细胞术和ELISA检测了PDT诱导的未成熟DC (imDCs)的表型和功能成熟。使用HNSCC细胞系SCC7建立了小鼠模型,并用于评估PDT-DC疫苗在促进PD-L1抗体抗肿瘤免疫中的治疗效果。
SCC7细胞的免疫原性细胞死亡(ICD)由0.5 µM m-THPC和5 J/cm²光剂量的PDT诱导。SCC7细胞的ICD刺激了imDCs的成熟。体内实验表明,PDT-DC疫苗和抗PD-L1 mAb协同诱导了抗肿瘤免疫并抑制了肿瘤进展。
BACKGROUND: Immune checkpoint inhibitors are promising tools in combating several cancers, including head and neck squamous cell carcinoma (HNSCC). However, a substantial portion of HNSCC patients do not respond to PD-L1 antibody. Here we describe a photodynamic therapeutic (PDT) approach to enhance anti-tumor effects of the anti-PD-L1 antibody. METHODS: Phototoxicity of PDT was confirmed using fluorescence microscopy, Cell Counting Kit-8 (CCK-8), Enzyme Linked Immunosorbent Assay (ELISA) and flow cytometry analyses. Phenotypic and functional maturation of immature DCs (imDCs) induced by PDT were measured using flow cytometry and ELISA. A mouse model was established using the HNSCC line, SCC7, and was used to evaluate therapeutic effects of PDT-DC vaccine in facilitating anti-tumor immunity of PD-L1 antibody. RESULTS: Immunogenic cell death (ICD) of SCC7 cells was induced by PDT with 0.5 µM of m-THPC and the 5 J/cm 2 of light dose. ICD of SCC7 cells stimulated imDCs maturation. In vivo assays suggested that PDT-DC vaccine and anti-PD-L1 mAb synergistically induced anti-tumor immunity and suppressed tumor progression. CONCLUSION: PDT-DC vaccine enhances therapeutic effects of PD-L1 antibody, which might provide a novel approach for HNSCC immunotherapy.
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