ArticleNature communications2025
A covalent peptide-based lysosome-targeting protein degradation platform for cancer immunotherapy.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- Lysosome-directed targeted protein degradation technologies for overcoming cancer drug resistance: mechanisms, design principles, and therapeutic opportunities.Drug delivery · 2026Review
- Unlocking the "undruggable": current landscape and emerging frontiers in lysosomal receptor-mediated protein degradation.Drug delivery · 2026Review
- Cyano-modulated Zn(II)-Schiff base complexes for lysosome-targeted fluorescence imaging and pH-responsive camptothecin delivery.International journal of pharmaceutics: X · 2026Article
- Supramolecular Degraders: An Emerging Paradigm in Targeted Protein Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Eradication of MRSA biofilm-associated implant infections by low-immunogenic sustained-release lysostaphin fused to thermosensitive polypeptides.Nature communications · 2026Article
- A Plug-and-Play Platform for Customizing Multivalent Degraders and Degrader-Drug Conjugates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A High-Loading Zn Single-Atom Nanozyme Targets the Zn/HIF-1α/GLUT1 Axis to Disrupt Glucose Metabolic Reprogramming and Remodel the Tumor Immune Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- Tutorial: strategies for targeting organelles using nanoparticles.Nature protocols · 2026Review
- Nano-enabled spatially selective protein degradation modulates lactate metabolism to potentiate antitumor immunity in liver cancer.Nature nanotechnology · 2026Article
- Discovery of novel tumor-targeting peptide-oncolytic peptide based conjugates (PPCs): A new paradigm for targeted oncolytic-immunotherapy.Acta pharmaceutica Sinica. B · 2026Article
- Transferrin receptor 1: an emerging therapeutic target in cancer beyond iron metabolism.Cancer cell international · 2026Review
- Highly Active CuAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Induced-proximity therapeutics for targeted protein and RNA degradation: An organic chemistry Perspective-A review.Current research in structural biology · 2026Review
- Multispecific nanobody degraders co-deplete membrane receptors and enable targeted delivery of diverse payloads.bioRxiv : the preprint server for biology · 2026Article
- Molecular engineering of lysosome-based degraders unveils a rapidly expanding therapeutic strategy.Autophagy · 2026Review
- Tumor-Targeted Delivery Therapy Based on PLGA Nanoparticles.Journal of functional biomaterials · 2026Review
- Lysosome-centered nanomedicine for cancer therapy: mechanisms, materials, and modalities.Journal of nanobiotechnology · 2026Review
- The application of drug delivery systems based on targeted protein degradation chimeras in disease treatment strategies.Journal of nanobiotechnology · 2026Review
- Extracellular and Membrane Protein: Structure, Biological Functions, Diseases, and an Emerging Modality for Drug Discovery.MedComm · 2026Review
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
The lysosome-targeting chimera (LYTAC) strategy provided a very powerful tool for the degradation of membrane proteins. However, the synthesis of LYTACs, antibody-small molecule conjugates, is challenging. The ability of antibody-based LYTACs to penetrate solid tumor is limited as well, especially to cross the blood-brain barrier (BBB). Here, we propose a covalent chimeric peptide-based targeted degradation platform (Pep-TACs) by introducing a long flexible aryl sulfonyl fluoride group, which allows proximity-enabled cross-linking upon binding with the protein of interest. The Pep-TACs platform facilitates the degradation of target proteins through the mechanism of recycling transferrin receptor (TFRC)-mediated lysosomal targeted endocytosis. Biological experiments demonstrate that covalent Pep-TACs can significantly degrade the expression of PD-L1 on tumor cells, dendritic cells and macrophages, especially under acidic conditions, and markedly enhance the function of T cells and tumor phagocytosis by macrophages. Furthermore, both in anti-PD-1-responsive and -resistant tumor models, the Pep-TACs exert significant anti-tumor immune response. It is noteworthy that Pep-TACs can cross the BBB and prolong the survival of mice with in situ brain tumor. As a proof-of-concept, this study introduces a modular TFRC-based covalent peptide degradation platform for the degradation of membrane protein, and especially for the immunotherapy of brain tumors.
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Registered trials
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