目的了解肿瘤抗原肽的HLA限制性以及其诱导的T细胞能否杀伤肿瘤细胞,探索无关供者来源细胞用于过继性抗肿瘤T细胞治疗。方法使用16个肿瘤抗原肽诱导18名无关供者外周血单个核细胞(PBMC)分化为反应性T细胞,并分析HLA型别;利用NetMHC数据...目的了解肿瘤抗原肽的HLA限制性以及其诱导的T细胞能否杀伤肿瘤细胞,探索无关供者来源细胞用于过继性抗肿瘤T细胞治疗。方法使用16个肿瘤抗原肽诱导18名无关供者外周血单个核细胞(PBMC)分化为反应性T细胞,并分析HLA型别;利用NetMHC数据库预测肽和HLA分子亲和力;选择HLA-A2限制性的肿瘤抗原肽诱导第二组17名无关供者的PBMC进行杀瘤实验,反应性T细胞作为效应细胞,T2细胞及肿瘤抗原肽同源的肿瘤细胞作为靶细胞,测量LDH(乳酸脱氢酶)释放量或者RTCA(实时无标记细胞分析仪)检测效应细胞杀瘤效率,比较HLA-A2+和A2-T细胞杀瘤效率。结果筛出和HLA-A2具有高亲和力的肿瘤抗原肽LM7,可诱导5/11 HLA-A2+为反应性T细胞,其中HLA-A2+纯合子则为3/3,而HLA-A2-者则为2/7。LM7诱导反应性T细胞杀伤肿瘤百分比A2+组明显强于A2-组(60.72±11.28 vs 47.2±4.46,P=0.03)。结论本研究显示NetMHC预测对于纯合子样品更有帮助,肿瘤抗原肽LM7具有HLA-A2限制性,可诱导部分HLAA2+PBMC分化为反应性T细胞,可杀伤肿瘤,应对供者进行HLA筛选并分析其细胞功能,其诱导的反应性T细胞可作为过继性T细胞抗肿瘤治疗的细胞来源。展开更多
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
文摘目的了解肿瘤抗原肽的HLA限制性以及其诱导的T细胞能否杀伤肿瘤细胞,探索无关供者来源细胞用于过继性抗肿瘤T细胞治疗。方法使用16个肿瘤抗原肽诱导18名无关供者外周血单个核细胞(PBMC)分化为反应性T细胞,并分析HLA型别;利用NetMHC数据库预测肽和HLA分子亲和力;选择HLA-A2限制性的肿瘤抗原肽诱导第二组17名无关供者的PBMC进行杀瘤实验,反应性T细胞作为效应细胞,T2细胞及肿瘤抗原肽同源的肿瘤细胞作为靶细胞,测量LDH(乳酸脱氢酶)释放量或者RTCA(实时无标记细胞分析仪)检测效应细胞杀瘤效率,比较HLA-A2+和A2-T细胞杀瘤效率。结果筛出和HLA-A2具有高亲和力的肿瘤抗原肽LM7,可诱导5/11 HLA-A2+为反应性T细胞,其中HLA-A2+纯合子则为3/3,而HLA-A2-者则为2/7。LM7诱导反应性T细胞杀伤肿瘤百分比A2+组明显强于A2-组(60.72±11.28 vs 47.2±4.46,P=0.03)。结论本研究显示NetMHC预测对于纯合子样品更有帮助,肿瘤抗原肽LM7具有HLA-A2限制性,可诱导部分HLAA2+PBMC分化为反应性T细胞,可杀伤肿瘤,应对供者进行HLA筛选并分析其细胞功能,其诱导的反应性T细胞可作为过继性T细胞抗肿瘤治疗的细胞来源。
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。
文摘目的探讨人类白细胞抗原(human leukocyte antigen,HLA)基因多态性与乙型肝炎病毒(HBV)感染的相关性。方法收集云南省昆明市延安医院健康体检者静脉血样本501例,采用酶联免疫吸附试验(ELISA)检测HBV二对半,根据HBV二对半检测结果分为HBV携带组和既往感染组以及健康对照组3组,用序列特异性引物聚合酶链反应(polymerase chain reaction with sequence specific primers,PCR-SSP)基因分型技术检测HLA-A抗原的基因型,将HBV携带组和健康对照组以及HBV既往感染组和健康对照组的HLA-A基因多态性的分布频率进行比较。采用SPSS17.0软件进行数据统计分析。结果健康对照组HLA-A2阳性数占比47.49%,等位基因频率数占比31.29%;健康对照组基因分布频率总体与中华骨髓库发布的中国常见及确认的HLA-A等位基因表一致。HBV携带组HLA-A2阳性数占比63.04%,等位基因频率数占比42.23%,携带者的HLA-A2阳性率和等位基因频率差异有统计学意义(P<0.05);HBV既往感染组HLA-A2阳性数占比56.14%,等位基因频率数占比35.97%,既往感染组的HLA-A2阳性率和等位基因频率差异无统计学意义(P>0.05)。结论HLA-A2基因可能是慢性乙型肝炎HBV携带者的易感基因。
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.
