Engineering chimeric antigen receptor CD4 T cells for Alzheimer's disease

• 成果类型: Article
• 署名作者: Boskovic, Pavle; Shalita, Rotem; Gao, Wenqing; Vernon, Hailey; Deng, Yu Lin; Colonna, Marco; Majzner, Robbie G.; Amit, Ido; Kipnis, Jonathan
• 署名单位: Washington University (WUSTL); Washington University (WUSTL); Weizmann Institute of Science; Hong Kong University of Science & Technology; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; Dana-Farber Cancer Institute
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2530977123
• 发表日期: 2026-02-17
• 页码: e2530977123
• 关键词: chimeric antigen receptors; Alzheimer's disease; CART cells; T cell; neurodegeneration; pathology; memory; immunoglobulin; immunotherapy; immunization; lymphocytes; molecules; effector; therapy; plaques

摘要

Alzheimer's disease (AD) is the prevailing cause of age-associated dementia worldwide. Current standard of care relies on antibody-based immunotherapy. However, antibody-based approaches carry risks for patients, and their effects on cognition are marginal. Increasing evidence suggests that T cells contribute to AD onset and progression. Unlike the cytotoxic effects of CD8+ cells, CD4+ T cells capable of regulating inflammation show promise in reducing pathology and improving cognitive outcomes in mouse models of AD and in aging. Here, we sought to exploit the beneficial properties of CD4+ T cells while circumventing the need for TCR and peptide-MHC antigen discovery, thereby providing a potential universal therapeutic approach. To achieve this, forms of aggregated amyloid-f3. Our findings demonstrate that optimized CAR-T cells can alter amyloid deposition in the dura and reduce parenchymal pathology in the brain. Furthermore, we observed that CAR-T treatment promotes the expansion and CAR-T therapy not only to modify amyloid pathology but also to reshape the immune apies for neurodegenerative disease.