A Bispecific Peptide-Drug Conjugate Targeting LAG-3 and PD-L1 Harnesses Antitumor Immunity of Macrophages and T Cells - PubMed
6 hours ago
- #immune checkpoints
- #bispecific conjugate
- #cancer immunotherapy
- PD-1 and LAG-3 are key immune checkpoints on tumor-infiltrating macrophages and T cells.
- Blocking LAG-3 and PD-1 pathways can skew M2 macrophage polarization and show antitumor efficacy independent of T cells.
- A bispecific peptide-drug conjugate, BsPep-IMDQ, was developed to block both pathways and deliver a TLR7/8 agonist (IMDQ) via an MMP-cleavable linker.
- BsPep-IMDQ demonstrated potent tumor suppression in both anti-PD-1-responsive and -resistant tumor models.
- The conjugate promotes M1 macrophage polarization and CD8+ T-cell activation while minimizing systemic toxicity.
- Macrophage targeting is highlighted as a promising strategy for cancer immunotherapy.