Preclinical study demonstrates that myeloid-targeting nanobiologics reduce allograft fibrosis in a mouse lung transplant model, suggesting a novel immunosuppressive approach against chronic rejection.
Chronic lung allograft dysfunction (CLAD) is characterized by fibrotic graft remodeling and limits long-term survival after pulmonary transplantation. Despite clinical evidence that myeloid cells drive conditions that increase the risk of CLAD development, contemporary immunosuppression primarily targets lymphocytes. We evaluated an mTOR-inhibiting nanobiologic (mTORi-NB) targeting myeloid cells and their progenitors in a semiallogeneic mouse lung transplant model of CLAD. We found that the mTORi-NB preferentially targeted myeloid and endothelial cells in the allografts. Brief perioperative therapy with the mTORi-NBs reduced early macrophage graft infiltration and inhibited acute inflammation. In mTORi-NB-treated lung recipients, transcriptomic analysis revealed downregulation of fibrotic genes in macrophages and type I and type II (AT2) alveolar epithelial cells, known drivers of pulmonary fibrogenesis. We also observed upregulation of antifibrotic genes in macrophages after treatment with mTORi-NBs, as well as reduction of allograft fibrosis, associated with preservation of club and AT2 cells. Our findings suggest that myeloid-avid nanobiologics may be a promising immunosuppressive strategy for inhibiting CLAD.
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Mineura et al. (2026) studied this question.
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