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REVIEW article

Front. Immunol.

Sec. T Cell Biology

This article is part of the Research TopicHarnessing T Cell Effectors: From Mechanisms to TherapiesView all 6 articles

CAR T for Fighting IPF: Perspectives on a Living Drug

Provisionally accepted
Wei  SunWei Sun1Sirui  LuSirui Lu2Tao  ChenTao Chen2Yanrui  HeYanrui He2Zuojun  XuZuojun Xu2*Zhigang  CaiZhigang Cai1
  • 1Second Hospital of Hebei Medical University, Shijiazhuang, China
  • 2Peking Union Medical College Hospital, Beijing, China

The final, formatted version of the article will be published soon.

Fibrotic interstitial lung disease (fILD), particularly idiopathic pulmonary fibrosis (IPF), represents an incurable progressive lung disorder characterized by a dismal prognosis. Fibroblasts constitute the principal cellular drivers of the fibrotic cascade. Although two pharmacological agents (pirfenidone and nintedanib) have secured regulatory approval for clinical application, they remain incapable of substantially attenuating disease progression. Persistent immune dysregulation driven alveolitis, occupies a critical upstream position in perpetuating fibroblast activation and extracellular matrix (ECM). Recent investigations have introduced an innovative strategy employing genetically engineered T cells to selectively target and eliminate activated fibroblasts. This approach involves generating chimeric antigen receptor (CAR) T cells in vivo by encapsulating mRNA encoding CARs within lipid nanoparticles (LNPs). These CAR T cells can specifically recognize and ablate fibroblasts expressing fibroblast activation protein (FAP). In this review, we summarize recently developed CAR T cell therapeutic strategies for IPF treatment with optimal targeting of FAP-fibroblasts, synthesize the existing preclinical studies and clinical trials evaluating anti-FAP CAR T cells to date, and critically discuss the adverse events associated with CAR T therapy alongside strategies to overcome current limitations of CAR T cell therapy in IPF management.

Keywords: CAR T cell, fILD, ILD, IPF, therapy

Received: 17 Dec 2025; Accepted: 13 Feb 2026.

Copyright: © 2026 Sun, Lu, Chen, He, Xu and Cai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Zuojun Xu

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