ArticleNature biomedical engineering2025
Potentiating cancer immunotherapies with modular albumin-hitchhiking nanobody-STING agonist conjugates.
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Article in Nature biomedical engineering, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32citing papers in PubMed
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32 citing papers in PubMed.
- Microbiota-derived self-adjuvanting exopolysaccharide-based codelivery system for potent cancer immunotherapy.Materials today. Bio · 2026Article
- Polymeric Materials in Cancer Immunotherapy: Advances, Challenges, and Future Directions.Polymer science & technology (Washington, D.C.) · 2026Review
- αHSA-proIL-12: A Tumor-Conditional IL-12 Prodrug with Reduced Systemic Toxicity and Potent Antitumor Activity.International journal of molecular sciences · 2026Article
- MERTK inhibition cooperates with immunomodulatory cyclophosphamide to induce CXCL9⁺ monocyte-macrophage programming and durable antitumor immunity in triple negative breast cancer.Cancer immunology research · 2026Article
- Leveraging Mitochondria-Endoplasmic Reticulum Functional Interplay With an On-Demand Nanoparticle to Boost mtDNA-Based STING Immunotherapy.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Linker-directed lipid-antigen conjugates co-enhance lymph node targeting and antigen presentation for potent T cell immunity.Materials today. Bio · 2026Article
- Engineered GLUT1-targeted STING polyproagonists: Redox-triggered activation and enhanced endosomal escape for cancer immunotherapy.Asian journal of pharmaceutical sciences · 2026Article
- Label-Free Single Protein Dynamics Revealed by Metasurface-Enhanced Raman Spectroscopy.ACS nano · 2026Article
- Macrophage Extracellular Traps in Immunity and Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Fatty Acids in Cancer Therapy: Chemical Conjugates, Nanocarriers, and Therapeutic Opportunities.Molecules (Basel, Switzerland) · 2026Review
- Albumin-Bound STING Agonist Reprograms HSPCs to Antitumor Neutrophils Enhancing CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- From Neoantigens to Nanocarriers: Modern Methods and Modalities in Using Peptides for Cancer Vaccination.Biochemistry · 2026Review
- AND logic nanoparticle for precision immunotherapy of metastatic cancers.Nature nanotechnology · 2026Article
- Macrophages: Targets for next-generation cancer immunotherapy.Cancer cell · 2026Review
- Article
- Beyond conceptual advances in cancer therapies.Nature biomedical engineering · 2026Article
- Self-Assembled Nanoparticles with Kynureninase-Fc Fusion Protein and Pheophorbide A for Photodynamic Immunometabolic Cancer Therapy.Journal of functional biomaterials · 2026Article
- Engineered extracellular vesicles displaying bi-specific T-cell engagers for targeted therapy of B-cell malignancies.Experimental hematology & oncology · 2026Article
- MERTK inhibition cooperates with immunomodulatory cyclophosphamide to induce CXCL9bioRxiv : the preprint server for biology · 2026Article
- Review
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Authors and funding
25 authors.
Blaise R KimmelDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-9582-9887
Karan AroraDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.ORCID http://orcid.org/0000-0003-1472-1637
Neil C ChadaDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.ORCID http://orcid.org/0000-0003-4566-3564
Vijaya BhartiDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Alexander J KwiatkowskiDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.ORCID http://orcid.org/0000-0001-5435-3555
Jonah E FinkelsteinDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Ann HannaDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Emily N ArnerDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0003-3589-8829
Taylor L SheehyDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-3100-8115
Lucinda E PastoraDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Jinming YangDepartment of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA.
Hayden M PagendarmDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.ORCID http://orcid.org/0000-0001-7611-6120
Payton T StoneDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-8105-0610
Ebony Hargrove-WileyDepartment of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0003-4452-4917
Brandie C TaylorDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-4862-4678
Lauren A HubertDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA.
Barbara M FingletonDepartment of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA.
Katherine N Gibson-CorleyDivision of Comparative Medicine, Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-1846-1580
Jody C MayDepartment of Chemistry, Vanderbilt University, Nashville, TN, USA.ORCID http://orcid.org/0000-0003-4871-5024
John A McLeanDepartment of Chemistry, Vanderbilt University, Nashville, TN, USA.ORCID http://orcid.org/0000-0001-8918-6419
Jeffrey C RathmellVanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-4106-3396
Ann RichmondDepartment of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-9580-900X
W Kimryn RathmellDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-4984-0225
Justin M BalkoDepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-4263-5974
John T WilsonDepartment of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA. john.t.wilson@vanderbilt.edu.ORCID http://orcid.org/0000-0002-9144-2634
Funding
Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Ben Ho Park · 1995 to 2026
$172.8MTISSUE CoreP50CA098131 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PARK, BEN HO, PIETENPOL, JENNIFER A · 2003 to 2024
$48.7MTranslational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MARY Kay WASHINGTON · 2002 to 2026
$29.9MVanderbilt Diabetes Research CenterP30DK020593 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI OWEN P MCGUINNESS · 2012 to 2026
$29.3MMEDICAL SCIENTIST TRAINING PROGRAMT32GM007347 · NIGMS · VANDERBILT UNIVERSITY · PI WILLIAMS, CHRISTOPHER S. · 1985 to 2023
$26.3MShop Module CoreP30EY008126 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI David J. Calkins · 1989 to 2026
$19.6MVanderbilt Mouse Metabolic Physiology CenterU24DK059637 · NIDDK · VANDERBILT UNIVERSITY · PI WASSERMAN, DAVID H · 2001 to 2015
$14.9MMULTIDISCIPLINARY BASIC RESEARCH TRAINING IN CANCERT32CA009592 · NCI · VANDERBILT UNIVERSITY · PI Justin M Balko, Julie A Rhoades (Sterling) · 1987 to 2026
$10.4MChemistry-Biology Interface Training GrantT32GM065086 · NIGMS · VANDERBILT UNIVERSITY · PI BACHMANN, BRIAN O, SULIKOWSKI, GARY ALLEN · 2002 to 2022
$7.0MMedical Scientist Training ProgramT32GM152284 · NIGMS · VANDERBILT UNIVERSITY · PI Christopher S. Williams · 2024 to 2026
$4.8MMetabolic Barriers to T Cell Activation in Clear Cell Renal Cell CarcinomaR01CA217987 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jeffrey C Rathmell · 2018 to 2026
$4.3MIntegrated Training in Engineering and DiabetesT32DK101003 · NIDDK · VANDERBILT UNIVERSITY · PI Jamey D. Young · 2014 to 2026
$3.9MBLRD VA I01 BX002301National Science Foundation (NSF) 193793National Science Foundation (NSF) CBET-1554623National Science Foundation (NSF) DMR 1852157NCI NIH HHS F32 CA288044NCI NIH HHS K00 CA253718NCI NIH HHS P30 CA068485NCI NIH HHS P50 CA098131NCI NIH HHS R01 CA217987NCI NIH HHS R01 CA245134NCI NIH HHS R01 CA266767NCI NIH HHS R01 CA274675NCI NIH HHS T32 CA009592NEI NIH HHS P30 EY008126NIDDK NIH HHS P30 DK020593NIDDK NIH HHS P30 DK058404NIDDK NIH HHS T32 DK101003NIDDK NIH HHS U24 DK059637NIGMS NIH HHS T32 GM007347NIGMS NIH HHS T32 GM065086NIGMS NIH HHS T32 GM152284NIH HHS S10 OD021630Pharmaceutical Research and Manufacturers of America Foundation (PhRMA Foundation) Postdoctoral Fellowship in Drug DeliverySusan G. Komen (Susan G. Komen Breast Cancer Foundation) CCR19609205United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP) BC170037U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P30 CA68485U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01 CA11601U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) SPORE 2P50CA098131-17U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) T32CA009592U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) T32DK101003U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) T32GM007347U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) T32GM065086U.S. Department of Veterans Affairs (Department of Veterans Affairs) IK6B005225
Abstract
The enhancement of antitumour immunity via agonists of the stimulator of interferon genes (STING) pathway is limited by pharmacological barriers. Here we show that the covalent conjugation of a STING agonist to anti-albumin nanobodies via site-selective bioconjugation chemistries prolongs the circulation of the agonist in the blood and increases its accumulation in tumour tissue, stimulating innate immune programmes that increased the infiltration of activated natural killer cells and T cells, which potently inhibited the growth of mouse tumours. The technology is modular, as demonstrated by the recombinant integration of a second nanobody domain targeting programmed death-ligand 1 (PD-L1), which further increased the accumulation of the agonist in tumours while blocking immunosuppressive PD-1/PD-L1 interactions. The bivalent nanobody-STING agonist conjugate stimulated robust antigen-specific T-cell responses and long-lasting immunological memory and conferred enhanced therapeutic efficacy. It was also effective as a neoadjuvant treatment to adoptive T-cell therapy. As a modular approach, hitchhiking STING agonists on serum albumin may serve as a broadly applicable strategy for augmenting the potency of systemically administered cancer immunotherapies.
Indexed as
AlbuminsImmunotherapyMembrane ProteinsNeoplasmsSingle-Domain AntibodiesAnimalsB7-H1 AntigenCell Line, TumorFemaleHumansKiller Cells, NaturalMiceMice, Inbred C57BLSTING ProteinT-LymphocytesAlbuminsB7-H1 AntigenMembrane ProteinsSingle-Domain AntibodiesSTING1 protein, humanSting1 protein, mouseSTING Protein
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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.