解放军医学院学报2024，Vol.45Issue(8)：847-853,7.DOI:10.12435/j.issn.2095-5227.2024.101
卡铂与PD-1免疫检查点抑制剂最佳联合治疗时序的探索研究
Exploration of optimal timing of combining carboplatin with PD-1 immune checkpoint inhibitors
摘要
Abstract
Background Currently,chemotherapy combined with immunotherapy is being widely used in treating various types of tumors,but the optimal combination timing of the two is inconclusive.Objective To optimize the sequence and interval between carboplatin and PD-1 immune checkpoint inhibitors(ICIs),so as to minimize the toxic effect of this combination regimen on immune cells.Methods Human peripheral blood mononuclear cells(PBMCs)were cultured in vitro and activated by anti-CD3 antibody,and the time when the proliferation of PBMCs reached the most active state was determined.Carboplatin was added at this time point,and the PBMCs survival rate-carboplatin concentration curve was plotted.The"safe concentration"of carboplatin that makes the survival rate of PBMCs not less than 90%was calculated,and the time corresponding to the"safe concentration"of carboplatin according to the in vivo drug time curve of carboplatin in the literature was speculated.Under the condition of immunosuppression,the time required for PD-1 antibody to bring the PBMCs'proliferation of to the most active state was determined,and the optimal sequence and interval of PD-1 ICIs in combination with carboplatin was calculated.Results PBMCs reached maximum proliferation rate on day4 after activation by CD3 antibody.Carboplatin concentrations less than 3.981µmol/L had a low toxic effect on PBMCs in vitro.In the presence of PD-L1 protein,it took 96 h for the anti-PD-1 antibody to bring PBMCs to a maximal proliferation rate.Conclusion The order of administration of carboplatin first,followed by PD-1 immune checkpoint inhibitors is less toxic to autologous lymphocytes.If PD-1 monoclonal antibody is used first,followed by carboplatin,the interval between the two administrations shouldn't exceed 86 h,otherwise,carboplatin will be more toxic to lymphocytes.关键词
免疫检查点抑制剂/人外周血单个核细胞/卡铂/药物联合治疗/治疗时间窗Key words
immune checkpoint inhibitors/peripheral blood mononuclear cells/carboplatin/combination drugtherapy/door to treatment time分类
医药卫生引用本文复制引用
孙小惠,邵佳康,李珂,龚一心,张孟,邱鲁鹏,孙卓雅,焦顺昌..卡铂与PD-1免疫检查点抑制剂最佳联合治疗时序的探索研究[J].解放军医学院学报,2024,45(8):847-853,7.基金项目
国家自然科学基金面上项目(81972681) （81972681）
