肿瘤细胞治疗研究
英文原题：Scalable generation of hematopoietic stem cell-engineered off-the-shelf mono-specific cytotoxic T cells targeting solid tumors.
实体瘤的过继性T细胞治疗受到自体制造复杂性的限制，而在异体环境中还存在移植物抗宿主病（GvHD）、HLA限制和供者变异性等风险。
过继性 T 细胞疗法在实体瘤中的应用受到自体制造复杂性以及异体环境下移植物抗宿主病（GvHD）、HLA 限制和供者变异性等风险的限制。我们开发了一个可扩展、无饲养层的平台，将基因工程化的造血干/祖细胞（HSPC）分化为异体、NY-ESO-1 特异性细胞毒性 T（Allo ESO-T）细胞。针对实体瘤模型评估产品的表型、功能、肿瘤归巢和安全性，并与外周血单个核细胞（PBMC）来源的 TCR 工程化 T 细胞进行基准比较。Allo ESO-T 细胞表现出均一的细胞毒性表型，通过转基因 TCR 和自然杀伤受体实现双重肿瘤靶向。与 PBMC 来源的对应细胞相比，Allo ESO-T 细胞表现出更优的细胞毒性、选择性实体瘤归巢、持久的杀伤持续性以及对免疫逃逸的抵抗力。它们还保持较低的 GvHD 和细胞因子释放综合征风险，同时保留稳定的低免疫原性特征。这些发现确立了 HSPC 来源的 Allo ESO-T 细胞作为一种现货型、单特异性细胞毒性 T 细胞疗法，具有可扩展的制造、增强的疗效和改善的安全性，支持 Allo ESO-T 细胞在实体瘤中的广泛适用性。
Adoptive T cell therapy for solid tumors is limited by autologous manufacturing complexity and, in allogeneic settings, risks including graft-versus-host disease (GvHD), HLA restriction, and donor variability. We develop a scalable, feeder-free platform to differentiate gene-engineered hematopoietic stem and progenitor cells (HSPCs) into allogeneic, NY-ESO-1-specific cytotoxic T ( Allo ESO-T) cells. Product phenotype, function, tumor homing, and safety are assessed against solid tumor models and benchmarked to peripheral blood mononuclear cell (PBMC)-derived TCR-engineered T cells. Allo ESO-T cells display a uniform cytotoxic phenotype, with dual tumor targeting through a transgenic TCR and natural killer receptors. Relative to PBMC-derived counterparts, Allo ESO-T cells show superior cytotoxicity, selective solid-tumor homing, durable killing persistence, and resilience to immune evasion. They also maintain low GvHD and cytokine release syndrome risk, while retaining stable hypoimmunogenic features. These findings establish HSPC-derived Allo ESO-T cells as an off-the-shelf, mono-specific cytotoxic T cell therapy with scalable manufacturing, enhanced efficacy, and improved safety, which support broad applicability of Allo ESO-T cells across solid tumors.
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