CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
针对广泛 KRAS 热点新抗原的 T 细胞应答的生成，用于细胞治疗或 TCR 发现
英文原题：Generation of T cell responses against broad KRAS hotspot neoantigens for cell therapy or TCR discovery.
查看英文原题
Generation of T cell responses against broad KRAS hotspot neoantigens for cell therapy or TCR discovery.
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中文摘要
靶向Kirsten大鼠肉瘤（KRAS）新抗原的T细胞过继细胞治疗（ACT）能够驱动抗肿瘤免疫，但迄今为止仅聚焦于已知KRAS新抗原中的一小部分。在此，我们开发了一种从外周血开始的单一流程，可根据每个个体的人类白细胞抗原（HLA）谱，在体外启动并扩增针对任何KRAS新抗原的T细胞应答。我们在20名健康供者中实施了该流程，并针对47种评估的新抗原中的46种产生了T细胞应答。我们鉴定并克隆了150多种KRAS T细胞受体（TCR），其中最强的TCR与临床活性基准TCR具有相似的效力。通过该流程生成的T细胞能够在体外和体内减缓肿瘤生长。该方法可作为开发体外启动治疗产品的基础，或用于发现针对广泛KRAS新抗原的TCR文库。
展开英文摘要原文
Adoptive cell therapy (ACT) with T cells targeting Kirsten rat sarcoma (KRAS) neoantigens can drive anti-tumor immunity but has so far been focused on a small fraction of known KRAS neoantigens.
Here, we develop a single process starting from peripheral blood that can prime and expand T cell responses ex vivo to any KRAS neoantigen based on each individual's human leukocyte antigen (HLA) profile.
We conducted the process in 20 healthy donors and generated T cell responses to 46 of 47 evaluated neoantigens.
We identified and cloned more than 150 KRAS T cell receptors (TCRs), with the strongest TCRs having similar potency to clinically active benchmark TCRs. T cells generated through this process were able to slow tumor growth in vitro and in vivo. The approach could be used as the basis for the development of an ex vivo primed therapeutic or to discover a library of TCRs against a broad range of KRAS neoantigens.
论文信息
- 作者
- Conn BP、Dietze JL、Yee CJ、Hallisey MM、Ortiz-Caraveo I、van Buuren MM、Gaynor RB、Foley KC
- 第一作者单位
- BioNTech US, Cambridge, MA 02139, USA.United States
- 通讯作者单位
- BioNTech US, Cambridge, MA 02139, USA. Electronic address: vikram.juneja@biontech.us.United States
- 期刊
- Cell reports methods2025 May 19
- 原文标识
- PubMed 40359936 · DOI 10.1016/j.crmeth.2025.101049
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