肿瘤细胞治疗研究
英文原题：A multidimensional workflow profiling of allogeneic virus-specific T cell therapies reveals potency-linked signatures.
异体病毒特异性T细胞（VST）疗法具有独特优势，包括可扩展性、快速部署和生产一致性，并已在多项临床试验中显示出疗效。
异体病毒特异性T细胞（VST）疗法具有独特的优势，包括可扩展性、快速部署和生产一致性，并已在多项临床试验中显示出疗效。然而，识别具有高治疗潜力的VST产品仍是一大障碍。在此，我们提出了一种多维分析平台，整合了体外和体内抗病毒反应性、T细胞受体（TCR）库分析、基因表达谱分析、免疫表型分析以及人源化小鼠模型中的功能验证。从HLA多样化的健康供者中扩增的EB病毒（EBV）特异性T细胞 consistently 富集了靶向EBV编码抗原的TCR。转录组学和高维流式细胞术分析揭示了一种独特的效应相关特征。重要的是，这种整合方法发现了T细胞效力和效应功能的相关生物标志物，并在EBV驱动的B细胞淋巴瘤体内模型中得到了验证。这些发现建立了一个可扩展的框架，用于表征异体T细胞产品，并可能为体内疗效预测指标的开发提供信息。
Allogeneic virus-specific T cell (VST) therapies offer distinct advantages, including scalability, rapid deployment, and manufacturing consistency, and have demonstrated efficacy in multiple clinical trials. However, identifying VST products with high therapeutic potential remains a major hurdle. Here, we present a multidimensional analytical platform that integrates in vitro and in vivo anti-viral reactivity, T cell receptor (TCR) repertoire analysis, gene expression profiling, immunophenotyping, and functional validation in a humanized mouse model. Epstein-Barr virus (EBV)-specific T cells expanded from HLA-diverse healthy donors consistently enriched for TCRs targeting EBV-encoded antigens. Transcriptomic and high-dimensional flow cytometric analyses revealed a distinct effector-associated signature. Importantly, this integrative approach uncovered correlative biomarkers of T cell potency and effector function, validated in an in vivo model of EBV-driven B cell lymphoma. These findings establish a scalable framework for the characterization of allogeneic T cell products and may inform the development of predictive metrics for in vivo efficacy.
MEMBER ACCOUNT
登录成功会直接打开下一页。
