ArticleNature biomedical engineering2024
Synthetic cationic helical polypeptides for the stimulation of antitumour innate immune pathways in antigen-presenting cells.
Article in Nature biomedical engineering, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- Bacteria-mimicking cancer cells reprogram macrophages via multiple pattern recognition receptor pathways for cancer immunotherapy.Signal transduction and targeted therapy · 2026Article
- α-Helical peptides: design strategies and recent advances in biomedical applications.Journal of translational medicine · 2026Review
- Soft-Drug-Inspired MnSTF Nano-Adjuvant for Safe and Synergistic cGAS-STING Activation in Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.Military Medical Research · 2026Review
- Emerging Strategies for Antitumor Immunotherapy and Antiviral Defense Through the cGAS-STING Pathway.International journal of nanomedicine · 2026Review
- Polypeptide sono-adjuvant for ultrasound-activatable regulation of innate immunity and cancer vaccination therapy.Nature communications · 2025Article
- Metallic nanomedicine in cancer immunotherapy.Acta pharmaceutica Sinica. B · 2025Review
- A Multi-Threshold Micelle Improves Tumor Accumulation and STING Immunotherapy.Journal of the American Chemical Society · 2025Article
- Reprogramming cancer immunity with next-generation combination therapies.Frontiers in cell and developmental biology · 2025Review
- Nanomedicines harnessing cGAS-STING pathway: sparking immune revitalization to transform 'cold' tumors into 'hot' tumors.Molecular cancer · 2024Review
- A goldilocks computational protocol for inhibitor discovery targeting DNA damage responses including replication-repair functions.Frontiers in molecular biosciences · 2024Article
Corrections and comments
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Authors and funding
24 authors at 1 institution in 1 country.
Funding
Abstract
Intracellular DNA sensors regulate innate immunity and can provide a bridge to adaptive immunogenicity. However, the activation of the sensors in antigen-presenting cells (APCs) by natural agonists such as double-stranded DNAs or cyclic nucleotides is impeded by poor intracellular delivery, serum stability, enzymatic degradation and rapid systemic clearance. Here we show that the hydrophobicity, electrostatic charge and secondary conformation of helical polypeptides can be optimized to stimulate innate immune pathways via endoplasmic reticulum stress in APCs. One of the three polypeptides that we engineered activated two major intracellular DNA-sensing pathways (cGAS-STING (for cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes) and Toll-like receptor 9) preferentially in APCs by promoting the release of mitochondrial DNA, which led to the efficient priming of effector T cells. In syngeneic mouse models of locally advanced and metastatic breast cancers, the polypeptides led to potent DNA-sensor-mediated antitumour responses when intravenously given as monotherapy or with immune checkpoint inhibitors. The activation of multiple innate immune pathways via engineered cationic polypeptides may offer therapeutic advantages in the generation of antitumour immune responses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.