小柯机器人

德国慕尼黑大学附属医院Sebastian Kobold团队近期取得重要工作进展，他们研究利用单细胞转录组图谱指导CAR-T细胞治疗急性髓系白血病。相关研究成果2023年3月13日在线发表于《自然—生物技术》杂志上。

据介绍，嵌合抗原受体T细胞（CAR-T细胞）已成为B细胞恶性肿瘤患者的有力治疗选择，但由于缺乏安全靶点，尚未在治疗急性髓系白血病（AML）方面取得成功。

研究人员利用来自15名AML患者的500000多个单细胞和来自9名健康人组织的公开可用RNA测序数据图谱，以预测在恶性细胞上表达但在健康细胞（包括T细胞）上缺乏的靶抗原。借助这种高分辨率的单细胞表达方法，研究人员通过计算确定集落刺激因子1受体和分化簇86作为CAR-T细胞治疗AML的靶点。

总之，对这些已建立的CAR-T细胞的功能验证表明，在细胞系和人源性AML模型中，体外和体内的疗效都很好，对相关健康人体组织的脱靶毒性最小。这为进一步的临床开发提供了有力的依据。

附：英文原文

Title: Single-cell transcriptomic atlas-guided development of CAR-T cells for the treatment of acute myeloid leukemia

Author: Gottschlich, Adrian, Thomas, Moritz, Grnmeier, Ruth, Lesch, Stefanie, Rohrbacher, Lisa, Igl, Veronika, Briukhovetska, Daria, Benmebarek, Mohamed-Reda, Vick, Binje, Dede, Sertac, Mller, Katharina, Xu, Tao, Dhoqina, Dario, Mrkl, Florian, Robinson, Sophie, Sendelhofert, Andrea, Schulz, Heiko, Umut, yk, Kavaka, Vladyslav, Tsiverioti, Christina Angeliki, Carlini, Emanuele, Nandi, Sayantan, Strzalkowski, Thaddus, Lorenzini, Theo, Stock, Sophia, Mller, Philipp Jie, Drr, Janina, Seifert, Matthias, Cadilha, Bruno L., Brabenec, Ruben, Rder, Natalie, Rataj, Felicitas, Nesch, Manuel, Modemann, Franziska, Wellbrock, Jasmin, Fiedler, Walter, Kellner, Christian, Beltrn, Eduardo, Herold, Tobias, Paquet, Dominik, Jeremias, Irmela, von Baumgarten, Louisa, Endres, Stefan, Subklewe, Marion, Marr, Carsten, Kobold, Sebastian

Issue&Volume: 2023-03-13

Abstract: Chimeric antigen receptor T cells (CAR-T cells) have emerged as a powerful treatment option for individuals with B cell malignancies but have yet to achieve success in treating acute myeloid leukemia (AML) due to a lack of safe targets. Here we leveraged an atlas of publicly available RNA-sequencing data of over 500,000 single cells from 15 individuals with AML and tissue from 9 healthy individuals for prediction of target antigens that are expressed on malignant cells but lacking on healthy cells, including T cells. Aided by this high-resolution, single-cell expression approach, we computationally identify colony-stimulating factor 1 receptor and cluster of differentiation 86 as targets for CAR-T cell therapy in AML. Functional validation of these established CAR-T cells shows robust in vitro and in vivo efficacy in cell line- and human-derived AML models with minimal off-target toxicity toward relevant healthy human tissues. This provides a strong rationale for further clinical development.

DOI: 10.1038/s41587-023-01684-0

Source: https://www.nature.com/articles/s41587-023-01684-0

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
官方网址：https://www.nature.com/nbt/
投稿链接：https://mts-nbt.nature.com/cgi-bin/main.plex