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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, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Proteinvetenskap. 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 (engelsk)Inngår i: Nature Communications, E-ISSN 2041-1723, Vol. 15, nr 1, artikkel-id 9542Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
Nature Research , 2024. Vol. 15, nr 1, artikkel-id 9542
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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
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QC 20241122

Tilgjengelig fra: 2024-11-20 Laget: 2024-11-20 Sist oppdatert: 2025-02-20bibliografisk kontrollert

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

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