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A bispecific CD40 agonistic antibody allowing for antibody-peptide conjugate formation to enable cancer-specific peptide delivery, resulting in improved T proliferation and anti-tumor immunity in mice
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Engineering. Strike Pharma AB, Uppsala, Sweden.ORCID iD: 0009-0000-0579-3060
Strike Pharma AB, Uppsala, Sweden; Department of Pharmacy, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Strike Pharma AB, Uppsala, Sweden.
Strike Pharma AB, Uppsala, Sweden.
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2024 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 15, no 1, article id 9542Article in journal (Refereed) Published
Abstract [en]

Current antibody-based immunotherapy depends on tumor antigen shedding for proper T cell priming. Here we select a novel human CD40 agonistic drug candidate and generate a bispecific antibody, herein named BiA9*2_HF, that allows for rapid antibody-peptide conjugate formation. The format is designed to facilitate peptide antigen delivery to CD40 expressing cells combined with simultaneous CD40 agonistic activity. In vivo, the selected bispecific antibody BiA9*2_HF loaded with peptide cargos induces improved antigen-specific proliferation of CD8+ (10-15 fold) and CD4+ T cells (2-7 fold) over control in draining lymph nodes. In both virus-induced and neoantigen-based mouse tumor models, BiA9*2_HF demonstrates therapeutic efficacy and elevated safety profile, with complete tumor clearance, as well as measured abscopal impact on tumor growth. The BiA9*2_HF drug candidate can thus be utilized to tailor immunotherapeutics for cancer patients.

Place, publisher, year, edition, pages
Nature Research , 2024. Vol. 15, no 1, article id 9542
National Category
Immunology in the medical area Biochemistry Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cancer and Oncology
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URN: urn:nbn:se:kth:diva-356688DOI: 10.1038/s41467-024-53839-5ISI: 001348514000014PubMedID: 39500897Scopus ID: 2-s2.0-85208602407OAI: oai:DiVA.org:kth-356688DiVA, id: diva2:1914859
Note

QC 20241122

Available from: 2024-11-20 Created: 2024-11-20 Last updated: 2025-02-20Bibliographically approved

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Mebrahtu, AmanDahllund, LeifOlsson, AndersAndersson, OscarPersson, JonathanPersson, HelenaRockberg, Johan

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Mebrahtu, AmanDahllund, LeifOlsson, AndersAndersson, OscarPersson, JonathanPersson, HelenaRockberg, Johan
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Protein EngineeringDrug Discovery and DevelopmentScience for Life Laboratory, SciLifeLabProtein ScienceProtein Technology
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Nature Communications
Immunology in the medical areaBiochemistryMolecular BiologyMedical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)Cancer and Oncology

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