美国宾夕法尼亚大学Jonathan A. Epstein研究组发现体内产生的CAR T细胞可治疗心脏损伤。相关论文发表在2022年1月7日出版的《科学》杂志上。

他们开发了一种治疗方法，通过在 T 细胞靶向脂质纳米粒子 (LNP) 中递送修饰的信使 RNA (mRNA)，在体内产生瞬时抗纤维化嵌合抗原受体 (CAR) T 细胞。通过将靶向 CD5 的 LNP 注射到心力衰竭小鼠模型中，评估了这些体内重新编程的 CAR T 细胞的功效。

观察到编码 CAR 的修饰 mRNA 向 T 淋巴细胞的有效递送，这在体内产生了瞬时、有效的 CAR T 细胞。抗纤维化 CAR T 细胞在脾脏中积累时表现出吞噬作用并保留了靶抗原。用修饰的 mRNA 靶向 LNP 治疗可减少纤维化并恢复受伤后的心脏功能。CAR T 细胞的体内生成有望成为治疗各种疾病的治疗平台。

据了解，纤维化影响着数以百万计的心脏病患者。

附：英文原文

Title: CAR T cells produced in vivo to treat cardiac injury

Author: Joel G. Rurik, István Tombácz, Amir Yadegari, Pedro O. Méndez Fernández, Swapnil V. Shewale, Li Li, Toru Kimura, Ousamah Younoss Soliman, Tyler E. Papp, Ying K. Tam, Barbara L. Mui, Steven M. Albelda, Ellen Puré, Carl H. June, Haig Aghajanian, Drew Weissman, Hamideh Parhiz, Jonathan A. Epstein

Issue&Volume: 2022-01-07

Abstract: Fibrosis affects millions of people with cardiac disease. We developed a therapeutic approach to generate transient antifibrotic chimeric antigen receptor (CAR) T cells in vivo by delivering modified messenger RNA (mRNA) in T cell–targeted lipid nanoparticles (LNPs). The efficacy of these in vivo–reprogrammed CAR T cells was evaluated by injecting CD5-targeted LNPs into a mouse model of heart failure. Efficient delivery of modified mRNA encoding the CAR to T lymphocytes was observed, which produced transient, effective CAR T cells in vivo. Antifibrotic CAR T cells exhibited trogocytosis and retained the target antigen as they accumulated in the spleen. Treatment with modified mRNA-targeted LNPs reduced fibrosis and restored cardiac function after injury. In vivo generation of CAR T cells may hold promise as a therapeutic platform to treat various diseases.

DOI: abm0594

Source: https://www.science.org/doi/10.1126/science.abm0594