Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells.One of the most exciting advances withi...Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells.One of the most exciting advances within this field is the targeting of neoantigens,which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal cells.Although neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment,early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint inhibitors.Progress made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of neoantigens.Consequently,personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents recurrences.This review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines,and also discusses challenges and future perspectives for this innovative approach,particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.展开更多
目的分析血液病患者HLAⅠ类抗体微珠反应的平均荧光强度(MFI)与血小板输注疗效的关系。方法回顾性分析2021年1月至2022年10月中国科学技术大学附属第一医院(安徽省立医院)收治的68例血液病患者的临床资料,及血小板输注前HLAⅠ类抗体MFI...目的分析血液病患者HLAⅠ类抗体微珠反应的平均荧光强度(MFI)与血小板输注疗效的关系。方法回顾性分析2021年1月至2022年10月中国科学技术大学附属第一医院(安徽省立医院)收治的68例血液病患者的临床资料,及血小板输注前HLAⅠ类抗体MFI情况。依据血小板输注后24 h血小板计数增高指数(CCI)判定血小板输注疗效,并将患者分为有效组和无效组,logistic多因素回归模型分析血小板输注效果的影响因素,绘制受试者工作特征(ROC)曲线并计算曲线下面积(AUC)。根据AUC计算约登指数和其最大值,采用ROC曲线分析HLAⅠ类抗体对血小板输注无效(PTR)的预测作用。结果68例患者HLA抗体检测后输注血小板128次,其中有效输注98次,输注有效率76.56%,血小板无效输注30次,PTR发生率23.44%。单因素分析显示有效组和无效组在性别构成、HLAⅠ类抗体阳性占比、HLAⅡ类抗体阳性占比输注前后差值比较,差异有统计学意义(P<0.05);多因素分析显示HLAⅠ类抗体阳性为PTR危险因素(OR=9.64,95%CI:2.73~34.08,P<0.001);Pearson相关性检验得出HLAⅠ类抗体MFI与24 h CCI呈负相关(r=-0.369,P<0.01);根据所建立的预测模型绘制ROC曲线,曲线下面积为0.759(95%CI:0.619~0.898)。通过AUC计算约登指数最大值并得出最大截断值为MFI=531.6,灵敏度为75.00%,特异度为81.25%。结论HLAⅠ类抗体MFI作为预测血小板输注疗效的重要指标,可为临床选择合适血小板输注提供参考。展开更多
文摘目的 探讨免疫性血小板输注无效(PTR)患者HLA/HPA抗体特异性分布特征及其对血小板输注效果的影响。方法 本研究以86例免疫性PTR患者为研究对象,收集其性别、年龄、身高、体重、配血次数、疾病类型、输注前后血小板计数等临床资料,通过微珠法进行HLA特异性抗体的检测,并分析抗体特性对血小板输注效果的影响。结果 86例PTR患者中,单独HLA抗体、单独HPA抗体、HLA+HPA抗体阳性的患者分别为72例(83.72%)、8例(9.30%)、6例(6.98%)。HLA抗体在各位点中检出频率最高的抗体对应等位基因分别为A*25:01、B*15:12、C*02:02(和C*17:01),检出率分别为81.48%、87.04%、48.15%;而对应抗原表位出现频率最高的前三位为163LG、97V、71ATD,检出率分别为87.04%、77.78%、74.07%。仅存在HLA抗体的患者,输注交叉配型相合血小板的24 h血小板计数纠正增加指数(CCI)及输注有效情况均明显优于随机血小板(P<0.01)。在血小板交叉配型阴性结果的患者中,HLA抗体强度与交叉配型相合血小板的24 h CCI值及输注有效情况呈负相关关系,强度越高,输注效果越差(P<0.01)。HLA抗体强度为中、低等水平的患者,输注交叉配型相合血小板的24 h CCI值及输注有效情况均优于输注随机血小板(P<0.05)。结论 本研究所得到的PTR患者HLA/HPA抗体特性及其对血小板输注效果影响的结果,可为血小板库建立时供者的选择提供指导,同时对临床PTR患者的治疗方式选择有一定的参考价值。
基金supported by grants from the National Clinical Research Center Cancer Fundthe Haihe Laboratory of Synthetic Biology(22HHSWSS00004)。
文摘Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells.One of the most exciting advances within this field is the targeting of neoantigens,which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal cells.Although neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment,early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint inhibitors.Progress made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of neoantigens.Consequently,personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents recurrences.This review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines,and also discusses challenges and future perspectives for this innovative approach,particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.
文摘目的分析血液病患者HLAⅠ类抗体微珠反应的平均荧光强度(MFI)与血小板输注疗效的关系。方法回顾性分析2021年1月至2022年10月中国科学技术大学附属第一医院(安徽省立医院)收治的68例血液病患者的临床资料,及血小板输注前HLAⅠ类抗体MFI情况。依据血小板输注后24 h血小板计数增高指数(CCI)判定血小板输注疗效,并将患者分为有效组和无效组,logistic多因素回归模型分析血小板输注效果的影响因素,绘制受试者工作特征(ROC)曲线并计算曲线下面积(AUC)。根据AUC计算约登指数和其最大值,采用ROC曲线分析HLAⅠ类抗体对血小板输注无效(PTR)的预测作用。结果68例患者HLA抗体检测后输注血小板128次,其中有效输注98次,输注有效率76.56%,血小板无效输注30次,PTR发生率23.44%。单因素分析显示有效组和无效组在性别构成、HLAⅠ类抗体阳性占比、HLAⅡ类抗体阳性占比输注前后差值比较,差异有统计学意义(P<0.05);多因素分析显示HLAⅠ类抗体阳性为PTR危险因素(OR=9.64,95%CI:2.73~34.08,P<0.001);Pearson相关性检验得出HLAⅠ类抗体MFI与24 h CCI呈负相关(r=-0.369,P<0.01);根据所建立的预测模型绘制ROC曲线,曲线下面积为0.759(95%CI:0.619~0.898)。通过AUC计算约登指数最大值并得出最大截断值为MFI=531.6,灵敏度为75.00%,特异度为81.25%。结论HLAⅠ类抗体MFI作为预测血小板输注疗效的重要指标,可为临床选择合适血小板输注提供参考。
文摘目的为HLA和CD36复合抗体所致血小板输注无效(PTR)患者寻求相合或相容的供者血小板输注。方法采用ELISA方法检测PTR患者的血小板抗体及HLA⁃Ⅰ类抗体特异性;运用MATCH IT!和HLA Matchmaker软件,分析患者HLA⁃Ⅰ类抗体特异性及相应抗原决定簇(epitopes);采用HLA⁃SSO分型技术,获得供、患者的HLA基因型;根据HLA⁃I类抗原交叉反应组(CREG)或HLA表位配型(Eplet)策略,寻找与PTR患者相合或相容的供者血小板;通过血小板抗原单克隆抗体特异性免疫固定检测技术(MAIPA)和血小板免疫荧光流式检测(PIFT)鉴定匹配程度;最后,通过血小板计数纠正增加指数(CCI)评估血小板输注效果。结果2名PTR患者体内检测到针对HLA⁃Ⅰ类和CD36的复合抗体,且CD36流式表型为Ⅰ型缺失;抗体特异性检测结果显示,患者1和患者2的血清中存在高频的HLA⁃Ⅰ类抗体,PRA分别为56%(54/96)和53%(51/96);运用HLA的CREG和Eplet配型策略,在CD36缺失供者库分别筛选到与患者1匹配等级C的供者1名,与患者2匹配等级D的供者1名,且选择的供者均规避患者HLA⁃Ⅰ类抗体表位所针对的抗原;MAIPA和PIFT结果亦证实患者与供者血小板无免疫反应,且患者2输注相容血小板24 h CCI>4.5。结论针对HLA和CD36复合抗体所致PTR患者,可联合运用血清学交叉配型、HLA⁃CREG及Eplet配型策略,选择CD36缺失,规避HLA⁃Ⅰ类抗体对应抗原且HLA表位匹配的供者血小板。
