ArticleCell reports2022
Engineered human cytokine/antibody fusion proteins expand regulatory T cells and confer autoimmune disease protection.
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Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37citing papers in PubMed
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37 citing papers in PubMed, 43 citations in OpenAlex.
- Regulatory T cell induction strategies and applications in the treatment of immune and non-immune diseases.Signal transduction and targeted therapy · 2026Review
- Data-centric feedback loops for next-generation immunotherapy development.Nature biomedical engineering · 2026Review
- Engineering trispecific IL-2 receptor agonistic antibodies through geometry optimization for enhanced Treg targeting.Nature communications · 2026Article
- Taming immune responses to AAV gene therapy by programmed in vivo Treg expansion.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Targeting tumor-specific T cells with LAG3-directed interleukin-2 prevents T-cell exhaustion and reinvigorates antitumor immunity.Signal transduction and targeted therapy · 2026Article
- DC-CD4 bispecific tolerogenic nanovesicles induce antigen-specific regulatory T cells and ameliorate collagen-induced arthritis in mice.Nature communications · 2026Article
- Regulatory T cells in autoimmune diseases: biological mechanisms, clinical translation, and translational challenges.Frontiers in immunology · 2026Review
- Miniaturized IL-2/anti-IL-2 immunocytokines selectively activate and support theFrontiers in immunology · 2026Article
- Dynamics and variegation in the Treg response to Interleukin-2.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Regulatory T cells in homeostasis and disease: molecular mechanisms and therapeutic potential.Signal transduction and targeted therapy · 2025Review
- Temporal optimization of CD25-biased IL-2 agonists and immune checkpoint blockade leads to synergistic anticancer activity despite robust regulatory T cell expansion.Journal for immunotherapy of cancer · 2025Article
- IL-7 Immunotherapies: Current Applications and Engineering Opportunities.Immunological investigations · 2025Review
- An engineered Treg selective immunocytokine induces sustained immune modulation in a preclinical model of hemophilia A.Journal of thrombosis and haemostasis : JTH · 2025Article
- Metabolic reprogram and T cell differentiation in inflammation: current evidence and future perspectives.Cell death discovery · 2025Review
- Redirecting immune signaling with cytokine adaptors.Nature communications · 2025Article
- Harnessing the biology of regulatory T cells to treat disease.Nature reviews. Drug discovery · 2025Review
- Regulating IL-2 Immune Signaling Function Via A Core Allosteric Structural Network.Journal of molecular biology · 2025Article
- A facile yeast-display approach for antibody mask discovery.Protein engineering, design & selection : PEDS · 2025Article
- Cytokine Couture: Designer IL2 Molecules for the Treatment of Disease.ImmunoTargets and therapy · 2025Review
- Engineered cytokine/antibody fusion proteins improve IL-2 delivery to pro-inflammatory cells and promote antitumor activity.JCI insight · 2024Article
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Authors and funding
25 authors at 7 institutions in 3 countries.
Derek VanDykeDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Marcos IglesiasVascularized Composite Allotransplantation Laboratory, Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jakub TomalaInstitute of Biotechnology of the Academy of Sciences of the Czech Republic, Vestec 252 50, Czech Republic.
Arabella YoungDiabetes Center, University of California San Francisco, San Francisco, CA 94143, USA; Sean N. Parker Autoimmune Research Laboratory, University of California San Francisco, San Francisco, CA 94143, USA; Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA; Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Jennifer SmithDiabetes Center, University of California San Francisco, San Francisco, CA 94143, USA.
Joseph A PerryDepartment of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Edward GebaraTranslational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Amy R CrossTranslational Research Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX3 9DU, UK.
Laurene S CheungBloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD 21231, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21231, USA.
Arbor G DykemaBloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD 21231, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21231, USA.
Brian T Orcutt-JahnsDepartment of Bioengineering, Jonsson Comprehensive Cancer Center, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Tereza HenclováInstitute of Biotechnology of the Academy of Sciences of the Czech Republic, Vestec 252 50, Czech Republic.
Jaroslav GoliasInstitute of Microbiology of the Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic.
Jared BalolongDiabetes Center, University of California San Francisco, San Francisco, CA 94143, USA.
Luke M TomasovicDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
David FundaInstitute of Microbiology of the Academy of Sciences of the Czech Republic, Prague 142 20, Czech Republic.
Aaron S MeyerDepartment of Bioengineering, Jonsson Comprehensive Cancer Center, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Drew M PardollBloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD 21231, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21231, USA.
Joanna HesterTranslational Research Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX3 9DU, UK.
Fadi IssaTranslational Research Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX3 9DU, UK.
Christopher A HunterDepartment of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mark S AndersonDiabetes Center, University of California San Francisco, San Francisco, CA 94143, USA.
Jeffrey A BluestoneDiabetes Center, University of California San Francisco, San Francisco, CA 94143, USA; Sean N. Parker Autoimmune Research Laboratory, University of California San Francisco, San Francisco, CA 94143, USA; Sonoma Biotherapeutics, South San Francisco, CA 94080, USA.
Giorgio RaimondiVascularized Composite Allotransplantation Laboratory, Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jamie B SpanglerDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD 21231, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21231, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address: jamie.spangler@jhu.edu.
Johns Hopkins University · USUniversity of California, San Francisco · USBloomberg (United States) · USCzech Academy of Sciences · CZUniversity of Oxford · GBUniversity of California, Los Angeles · USUniversity of Pennsylvania · US
Funding
IMMUNOBIOLOGY OF NORMAL AND NEOPLASTIC LYMPHOCYTEST32CA009140 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Malay Haldar, WARREN S PEAR · 1985 to 2026
$16.1MMedical Scientist Training ProgramT32GM136577 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI ANDREA L COX · 2020 to 2026
$13.4MIMMUNOPATHOGENESIS OF TOXOPLASMIC ENCEPHALITISR01AI041158 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HUNTER, CHRISTOPHER A · 1996 to 2019
$4.8MImpact of early T-bet on CD8 T cell effector responsesR01AI125563 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HUNTER, CHRISTOPHER A · 2016 to 2020
$2.0MImmunoengineered nanotechnology for targeted expansion of regulatory T cellsR01EB029455 · NIBIB · JOHNS HOPKINS UNIVERSITY · PI SPANGLER, JAMIE BERTA · 2020 to 2023
$1.7MMapping the effector response space of antibody combinationsU01AI148119 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MEYER, AARON SAMUEL, NIMMERJAHN, FALK · 2020 to 2024
$1.6MDeveloping strategies to inhibit cancer immunotherapy-induced immune-related adverse events without impeding anti-tumor immunityK99CA246061 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YOUNG, ARABELLA · 2020 to 2021
$251kMedical Research Council MC_PC_17174Medical Research Council MC_PC_18059Medical Research Council MR/N027930/1NCI NIH HHS K99 CA246061NCI NIH HHS T32 CA009140NIAID NIH HHS R01 AI041158NIAID NIH HHS R01 AI125563NIAID NIH HHS U01 AI148119NIBIB NIH HHS R01 EB029455NIGMS NIH HHS T32 GM136577Wellcome Trust
Abstract
Low-dose human interleukin-2 (hIL-2) treatment is used clinically to treat autoimmune disorders due to the cytokine's preferential expansion of immunosuppressive regulatory T cells (Tregs). However, off-target immune cell activation and short serum half-life limit the clinical potential of IL-2 treatment. Recent work showed that complexes comprising hIL-2 and the anti-hIL-2 antibody F5111 overcome these limitations by preferentially stimulating Tregs over immune effector cells. Although promising, therapeutic translation of this approach is complicated by the need to optimize dosing ratios and by the instability of the cytokine/antibody complex. We leverage structural insights to engineer a single-chain hIL-2/F5111 antibody fusion protein, termed F5111 immunocytokine (IC), which potently and selectively activates and expands Tregs. F5111 IC confers protection in mouse models of colitis and checkpoint inhibitor-induced diabetes mellitus. These results provide a roadmap for IC design and establish a Treg-biased immunotherapy that could be clinically translated for autoimmune disease treatment.
Indexed as
Autoimmune DiseasesInterleukin-2AnimalsAntibodiesCytokinesHumansMiceT-Lymphocytes, RegulatoryAntibodiesCytokinesInterleukin-2antibodyautoimmune diseaseCP: Immunologycytokineimmunocytokineinterleukin-2molecular therapeuticsregulatory T cell
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