Evidence map›Paper›PMID 41004565›Full record

ArticleScience immunology2025

Design of a potent interleukin-21 mimic for cancer immunotherapy.

Jung-Ho Chun, Birkley S Lim, Suyasha Roy, Michael J Walsh, Gita C Abhiraman, Kevin Zhangxu, Tavus Atajanova, Or-Yam Revach, Elisa C Clark, Peng Li and 34 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Covalent tumor anchoring spatially orchestrates antitumor immunity.bioRxiv : the preprint server for biology · 2026
    Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

44 authors.

Jung-Ho ChunInstitute for Protein Design, University of Washington, Seattle, WA, USA.ORCID 0000-0003-4778-4175
Birkley S LimDepartment of Medicine, Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.ORCID 0009-0005-7558-9168
Suyasha RoyLaboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-0332-4962
Michael J WalshDepartment of Medicine, Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0002-1283-6847
Gita C AbhiramanDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-0546-4133
Kevin ZhangxuDepartment of Medicine, Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0002-7477-6691
Tavus AtajanovaDepartment of Medicine, Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.
Or-Yam RevachMass General Cancer Center, Krantz Family Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-1606-7467
Elisa C ClarkDepartment of Bioengineering and Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.
Peng LiLaboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Claire A PalinMass General Cancer Center, Krantz Family Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Asheema KhannaBen Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA.
Samantha TowerBen Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA.ORCID 0000-0001-7279-3079
Rakeeb KureshiDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0003-2769-2468
Megan T HoffmanDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0003-0907-9977
Tatyana SharovaMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-2123-3906
Aleigha LawlessMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.ORCID 0009-0009-3861-3164
Sonia CohenMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Genevieve M BolandBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-7522-6173
Tina NguyenInstitute for Protein Design, University of Washington, Seattle, WA, USA.ORCID 0009-0001-8385-0275
Frank PeprahDepartment of Medicine, Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.ORCID 0009-0004-6213-487X
Julissa G TelloDepartment of Medicine, Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.ORCID 0009-0009-7866-7327
Samantha Y LiuDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0009-0007-6837-5860
Chan Johng KimInstitute for Protein Design, University of Washington, Seattle, WA, USA.ORCID 0000-0002-7256-0205
Hojeong ShinInstitute for Protein Design, University of Washington, Seattle, WA, USA.ORCID 0000-0001-5895-0955
Alfredo Quijano-RubioInstitute for Protein Design, University of Washington, Seattle, WA, USA.ORCID 0000-0003-1567-9530
Kevin M JudeDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-3675-5136
Stacey GerbenInstitute for Protein Design, University of Washington, Seattle, WA, USA.ORCID 0000-0003-0313-6248
Analisa MurrayInstitute for Protein Design, University of Washington, Seattle, WA, USA.ORCID 0000-0003-1560-6673
Piper HeineInstitute for Protein Design, University of Washington, Seattle, WA, USA.ORCID 0009-0000-2220-8580
Michelle DeWittInstitute for Protein Design, University of Washington, Seattle, WA, USA.
Umut Y UlgeInstitute for Protein Design, University of Washington, Seattle, WA, USA.ORCID 0000-0002-3745-0668
Lauren CarterInstitute for Protein Design, University of Washington, Seattle, WA, USA.ORCID 0000-0002-9837-9068
Neil P KingInstitute for Protein Design, University of Washington, Seattle, WA, USA.ORCID 0000-0002-2978-4692
Daniel-Adriano SilvaInstitute for Protein Design, University of Washington, Seattle, WA, USA.ORCID 0000-0002-3195-9009
Hao Yuan KuehDepartment of Bioengineering and Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.ORCID 0000-0001-6272-6673
Vandana KaliaBen Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA.
Surojit SarkarBen Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA.ORCID 0000-0003-1940-1878
Russell W JenkinsMass General Cancer Center, Krantz Family Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-6110-2148
K Christopher GarciaDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.
Warren J LeonardLaboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-5740-7448
Michael DouganDepartment of Medicine, Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0001-9266-2009
Stephanie K DouganDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-2263-363X
David BakerInstitute for Protein Design, University of Washington, Seattle, WA, USA.ORCID 0000-0001-7896-6217

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007365 · NIGMS · STANFORD UNIVERSITY · PI CHUA, KATRIN F · 1985 to 2021
$33.8M
Structure-based engineering of immune cytokine signalingR01AI051321 · NIAID · STANFORD UNIVERSITY · PI Kenan Christopher GARCIA · 2002 to 2026
$5.6M
Stromal modulation of pancreatic cancer malignant cell state and therapeutic sensitivityU01CA274276 · NCI · DANA-FARBER CANCER INST · PI Andrew James Aguirre, Stephanie Dougan · 2022 to 2026
$5.1M
Mechanisms of T Cell Quiescence and ExhaustionR01AI132819 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI Surojit Sarkar · 2019 to 2026
$5.0M
Immunoregulatory Mechanisms of BiTE Efficacy in the Cold Neuroblastoma TMEU01CA281848 · NCI · SEATTLE CHILDREN'S HOSPITAL · PI Vandana Kalia, JAMES M OLSON · 2023 to 2026
$3.5M
Strategies for Receptor inhibition in immunotherapyR01CA177684 · NCI · STANFORD UNIVERSITY · PI DOUGAN, MICHAEL LAWRENCE, GARCIA, KENAN CHRISTOPHER · 2014 to 2025
$3.5M
De Novo Design of Minibinder Antagonists for COVID-19 and Future PandemicsR01AI160052 · NIAID · UNIVERSITY OF WASHINGTON · PI BAKER, DAVID, FULLER, DEBORAH H. · 2021 to 2025
$3.5M
Molecular Pathways Regulating Tissue-resident Memory T cells in the GutR01AI169188 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Michael Lawrence Dougan · 2022 to 2026
$3.0M
CDK4/6 inhibition during CD8 T cell priming potentiates memory formation in mice and humansR01AI158488 · NIAID · DANA-FARBER CANCER INST · PI DOUGAN, STEPHANIE · 2021 to 2025
$2.2M
Design of de novo interleukin mimics for targeted immunotherapyR01CA240339 · NCI · UNIVERSITY OF WASHINGTON · PI BAKER, DAVID · 2019 to 2023
$2.1M
Input encoding in T-cell receptor signalingR21EB027327 · NIBIB · UNIVERSITY OF WASHINGTON · PI KUEH, HAO YUAN · 2019 to 2021
$622k
Howard Hughes Medical InstituteNCI NIH HHS P30 CA015704NCI NIH HHS R01 CA177684NCI NIH HHS R01 CA240339NCI NIH HHS U01 CA274276NCI NIH HHS U01 CA281848NIAID NIH HHS R01 AI051321NIAID NIH HHS R01 AI132819NIAID NIH HHS R01 AI158488NIAID NIH HHS R01 AI160052NIAID NIH HHS R01 AI169188NIAID NIH HHS R21 AI154363NIA NIH HHS R56 AG069194NIBIB NIH HHS R21 EB027327NIGMS NIH HHS T32 GM007365
6 · The paper itself

Abstract

Long-standing goals of cancer immunotherapy are to activate cytotoxic antitumor T cells across a range of affinities for tumor antigens while suppressing regulatory T cells. Computational protein design has enabled the precise tailoring of proteins to meet specific needs. Here, we report a de novo designed IL-21 mimic, 21h10, with high stability and signaling potency in humans and mice. In murine and ex vivo human organotypic tumor models, 21h10 showed robust antitumor activity, with more prolonged signaling and stronger antitumor activity than native IL-21. 21h10 induced pancreatitis that could be mitigated by TNF blockade without compromising antitumor efficacy. Although antidrug antibodies to 21h10 formed, they were not neutralizing. 21h10 induced highly cytotoxic T cells with a range of affinities, robustly expanding intratumoral low-affinity cytotoxic T cells and driving high expression of IFN-γ and granzyme B compared with native IL-21, while increasing the frequency of IFN-γ

Indexed as

ImmunotherapyInterleukinsNeoplasmsAnimalsCell Line, TumorFemaleHumansInterleukin-21MiceMice, Inbred C57BLT-Lymphocytes, CytotoxicInterleukin-21Interleukins

Identifiers

PMID41004565
PMCPMC12768534

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