ArticleCell2019
An Allosteric Anti-tryptase Antibody for the Treatment of Mast Cell-Mediated Severe Asthma.
Erratum issuedOpen access · bronzeAbstract read
In one paragraph
Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 60 papers.
0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
8.7field-weighted citation impact, top 2% of its field
What it found
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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.
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Who cites it
60 citing papers in PubMed, 108 citations in OpenAlex.
- Dose-dependent inactivation of airway tryptase with a novel dissociating anti-tryptase antibody (MTPS9579A) in healthy participants: A randomized trial.Clinical and translational science · 2022Trial
- Understanding Tryptase Physiology, Clinical Significance, and Diagnostic Applications: Where Do We Stand?Biomolecules · 2026Review
- Mast cell proteases and their significance in physiology, pathology, and therapeutic approaches.Pharmacological reviews · 2026Review
- Complete inhibition of β-tryptase by tetramer dissociation and active site allostery due to a single antibody residue.Nature communications · 2026Article
- Distinct Tryptase Gene Copy Number Variations Correlate With Tryptase Levels in a Population-Based Cohort.Allergy · 2026Article
- Structural Basis of Serine Protease Inhibition by Antibodies from Biased Fab Phage-Display Libraries.bioRxiv : the preprint server for biology · 2026Article
- Melatonin: a promising therapy to combat type 2 airway inflammation via MT1-Sirt1 pathway.Frontiers in pharmacology · 2026Article
- MRGPRX2-expressing mast cells are increased in the GI tract of individuals with active inflammatory bowel disease and hereditary α-tryptasemia.medRxiv : the preprint server for health sciences · 2025Article
- Hereditary alpha tryptasemia and clinical implications.World journal of clinical cases · 2025Review
- Identification and validation of SAC3D1 as a prognostic biomarker promoting the development of osteosarcoma.Scientific reports · 2025Article
- Isolation of Allosteric Tryptase Inhibitor from Methanol Extract of Rhubarb and Enhancement of Its Tryptase Inhibitory Activity by Compounds That Were Screened by In Silico Screening.Molecules (Basel, Switzerland) · 2025Article
- Asthma, social isolation and loneliness, and risk of incident osteoarthritis.Arthritis research & therapy · 2025Article
- Mast cells: key players in digestive system tumors and their interactions with immune cells.Cell death discovery · 2025Review
- MRGPRX2-expressing mast cells are increased in the GI tract of individuals with active inflammatory bowel disease and hereditary α-tryptasemia.Frontiers in allergy · 2025Article
- Four-week IgE/baseline IgE ratio combined with tryptase predicts clinical outcome in omalizumab-treated children with moderate-to-severe asthma.Open medicine (Warsaw, Poland) · 2025Article
- Mast Cells in Allergic and Non-Allergic Upper Airways Diseases: Sentinel in the Watchtower.International journal of molecular sciences · 2024Review
- Computational modeling of mast cell tryptase family informs selective inhibitor development.iScience · 2024Article
- Alpha-Tryptase as a Risk-Modifying Factor for Mast Cell-Mediated Reactions.Current allergy and asthma reports · 2024Review
- Article
- Biomarkers of type 2 and non-type 2 inflammation in asthma exacerbations.Central-European journal of immunology · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
50 authors at 5 institutions in 3 countries.
Henry R MaunDepartment of Early Discovery Biochemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Janet K JackmanDepartment of Immunology Discovery, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
David F ChoyDepartment of Biomarker Discovery OMNI, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Kelly M LoyetDepartment of Biochemical and Cellular Pharmacology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Tracy L StatonDepartment of OMNI Biomarker Development, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Guiquan JiaDepartment of Biomarker Discovery OMNI, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Amy DressenDepartment of Human Genetics, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Jason A HackneyDepartment of Bioinformatics, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Meire BremerDepartment of OMNI Biomarker Development, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Benjamin T WaltersDepartment of Biochemical and Cellular Pharmacology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Rajesh VijDepartment of Antibody Engineering, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Xiaocheng ChenDepartment of Antibody Engineering, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Neil N TrivediDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
Ashley MorandoDepartment of Biochemical and Cellular Pharmacology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Michael T LipariDepartment of Early Discovery Biochemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Yvonne FrankeDepratment of Biomolecular Resources, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Xiumin WuDepartment of Translational Immunology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Juan ZhangDepartment of Translational Immunology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
John LiuDepartment of Translational Immunology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Ping WuDepartment of Structural Biology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Diana ChangDepartment of Human Genetics, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Luz D OrozcoDepartment of Bioinformatics, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Erin ChristensenDepartment of Protein Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Manda WongDepartment of Structural Biology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Racquel CorpuzDepartment of Structural Biology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Julie Q HangDepartment of Protein Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Jeff LutmanDepartment of Preclinical and Translational Pharmacokinetics, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Siddharth SukumaranDepartment of Preclinical and Translational Pharmacokinetics, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Yan WuDepartment of Antibody Engineering, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Savita UbhayakarDepartment of Drug Metabolism and Pharmacokinetics, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Xiaorong LiangDepartment of Drug Metabolism and Pharmacokinetics, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Lawrence B SchwartzDepartment of Internal Medicine, Division of Rheumatology, Allergy and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Magda BabinaDepartment of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Berlin, Germany.
Prescott G WoodruffDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
John V FahyDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Rahul AhujaDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
George H CaugheyDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
Aija KusiDepartment of Safety Assessment, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Mark S DennisDepartment of Antibody Engineering, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Charles EigenbrotDepartment of Structural Biology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Daniel KirchhoferDepartment of Early Discovery Biochemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Cary D AustinDepartment of Pathology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Lawren C WuDepartment of Immunology Discovery, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
James T KoerberDepartment of Antibody Engineering, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Wyne P LeeDepartment of Translational Immunology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Brian L YaspanDepartment of Human Genetics, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Kathila R AlatsisDepartment of Safety Assessment, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Joseph R ArronDepartment of Immunology Discovery, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: arron.joseph@gene.com.
Robert A LazarusDepartment of Early Discovery Biochemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: lazarus.bob@gene.com.
Tangsheng YiDepartment of Immunology Discovery, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: yi.tangsheng@gene.com.
Gene Therapy Laboratory · FRSan Francisco VA Medical Center · USUniversity of California, San Francisco · USCharité - Universitätsmedizin Berlin · DEVirginia Commonwealth University · US
Funding
Understanding Asthma EndotypesU19AI077439 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI David J Erle · 2008 to 2026
$41.1MRole of miRNAs in Th2-Driven inflammation in AsthmaP01HL107202 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FAHY, JOHN V · 2012 to 2023
$23.3MNHLBI NIH HHS P01 HL107202NIAID NIH HHS U19 AI077439
Abstract
Severe asthma patients with low type 2 inflammation derive less clinical benefit from therapies targeting type 2 cytokines and represent an unmet need. We show that mast cell tryptase is elevated in severe asthma patients independent of type 2 biomarker status. Active β-tryptase allele count correlates with blood tryptase levels, and asthma patients carrying more active alleles benefit less from anti-IgE treatment. We generated a noncompetitive inhibitory antibody against human β-tryptase, which dissociates active tetramers into inactive monomers. A 2.15 Å crystal structure of a β-tryptase/antibody complex coupled with biochemical studies reveal the molecular basis for allosteric destabilization of small and large interfaces required for tetramerization. This anti-tryptase antibody potently blocks tryptase enzymatic activity in a humanized mouse model, reducing IgE-mediated systemic anaphylaxis, and inhibits airway tryptase in Ascaris-sensitized cynomolgus monkeys with favorable pharmacokinetics. These data provide a foundation for developing anti-tryptase as a clinical therapy for severe asthma.
Indexed as
AdolescentAllosteric RegulationAnimalsAntibodies, Monoclonal, HumanizedAsthmaCell LineFemaleHumansMacaca fascicularisMaleMast CellsMiceMice, Inbred BALB CMice, Inbred NODMice, SCIDRabbitsAntibodies, Monoclonal, HumanizedTryptasesallosteric protease inhibitorantibody engineeringanti-IgEanti-tryptaseasthmamast cellnon-type 2 asthmaserine proteasetryptasetryptase genetics
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