Year: 2026
Type: article
Abstract: CAR-macrophage (CAR-M) therapy holds promise for the treatment of tumor and fibrotic diseases, yet genetic engineering remains the main efficacy-enhancing approach. Here we develop a non-genetic strategy using viscoelastic hydrogel to mechanically prime CAR-Ms. CAR-Ms exhibit potent phagocytosis of activated fibroblasts and collagen-degradation capacity, and hydrogel priming further enhances their cytotoxicity. Mechanistically, viscoelastic hydrogel priming reduces CAR-M membrane tension, which triggers membrane CAR to disassemble from clusters into dispersed monomers and dimers, leading to enhanced downstream signaling. In pulmonary fibrosis models, hydrogel-primed CAR-Ms demonstrate superior therapeutic outcomes, showing fibrosis reduction and microenvironment improvement. This study highlights CAR-M therapy’s potential for pulmonary fibrosis treatment and offers a distinct approach to improve CAR-M efficacy by physical stimuli. Pulmonary fibrosis is one of the most prevalent parenchymal fibrotic diseases. Here, Zhang et al. show that hydrogel priming enhances chimeric antigen receptor (CAR)-macrophage function, improving therapeutic efficacy in treating pulmonary fibrosis by a mechanical approach.
Source: Nature Communications
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: G3899533923, G6056758626, G718613278
OpenAlex ID: W7128795245