决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Beyond the hallmarks of cancer: enabling technologies reshaping cancer diagnosis, prevention, and treatment.
Beyond the hallmarks of cancer: enabling technologies reshaping cancer diagnosis, prevention, and treatment.
癌症生物学在过去20年中一直以标志性特征框架来组织,该框架于2000年提出,最近于2026年进行了修订。
癌症生物学在过去20年间由hallmarks框架组织,该框架于2000年提出,最近于2026年修订。肿瘤学技术变革的速度现在要求重新构建癌症检测、预防和治疗的方式。本综述认为,hallmarks框架虽然历史上至关重要,但已不再足以单独涵盖当代癌症诊疗,并将讨论重新定位于跨越并超越单个hallmark的使能技术。在诊断方面,多组学液体活检、AI辅助的影像组学和数字病理学、空间转录组学、单细胞测序以及血浆蛋白质组学的机器学习分析,现在支持更早期检测、在诊断前数年预测癌症风险、监测克隆演化以及预测治疗反应。在预防方面,人乳头瘤病毒和HBV疫苗在人群层面已验证的成功,与包括mRNA平台、CRISPR使能的抗原优化、个性化新抗原预防以及生物标志物分层的分子拦截在内的研究性方向形成对比,这些方向尚未在前瞻性人类癌症预防试验中得到验证。在治疗方面,讨论按治疗方式类别组织:免疫检查点抑制剂及耐药策略、抗体-药物偶联物、双特异性抗体和T细胞衔接器、放射性配体疗法、TIL(肿瘤浸润淋巴细胞)疗法、CRISPR编辑的CAR-T和TCR疗法、光子及光免疫疗法、RNA疗法以及适应性联合方案。比较表格总结了诊断平台、免疫治疗方式、光子疗法、CRISPR编辑的免疫治疗试验、新抗原疫苗管线以及融合策略。肿瘤学的发展轨迹将较少由对标志性特征的逐步完善来定义,而更多由将诊断、预防和治疗整合为连续的、数据驱动系统的融合技术来定义。
Cancer biology has been organized for 2 decades by the hallmarks framework, articulated in 2000 and most recently revised in 2026. The pace of technological change in oncology now requires reframing how cancer is detected, prevented, and treated. This review argues that the hallmarks framework, while historically essential, is no longer sufficient on its own to capture contemporary cancer care, and repositions the discussion around enabling technologies that operate across and beyond individual hallmarks. For diagnosis, multi-omic liquid biopsy, AI-assisted radiomics and digital pathology, spatial transcriptomics, single-cell sequencing, and machine-learning analysis of plasma proteomics now support earlier detection, prediction of cancer risk years before diagnosis, monitoring of clonal evolution, and prediction of treatment response. For prevention, the validated population-level success of Human papillomavirus and HBV vaccination is contrasted with investigational directions including mRNA platforms, CRISPR-enabled antigen optimization, personalized neoantigen prophylaxis, and biomarker-stratified molecular interception, none of which has yet been validated in prospective human cancer-prevention trials. For treatment, the discussion is organized by modality class: immune checkpoint inhibitors and resistance strategies, antibody-drug conjugates, bispecific antibodies and T-cell engagers, radioligand therapies, tumor-infiltrating lymphocyte therapy, CRISPR-edited CAR-T and TCR therapies, photonic and photoimmunologic therapies, RNA therapeutics, and adaptive combination regimens. Comparative tables summarize diagnostic platforms, immunotherapeutic modalities, photonic therapies, CRISPR-edited immunotherapy trials, neoantigen vaccine pipelines, and convergent strategies. The trajectory of oncology will be defined less by incremental refinement of hallmarks and more by convergent technologies that integrate diagnostics, prevention, and treatment into continuous, data-driven systems.
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