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 miceVisa övriga samt affilieringar
2024 (Engelska)Ingår i: Nature Communications, E-ISSN 2041-1723, Vol. 15, nr 1, artikel-id 9542Artikel i tidskrift (Refereegranskat) 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.
Ort, förlag, år, upplaga, sidor
Nature Research , 2024. Vol. 15, nr 1, artikel-id 9542
Nationell ämneskategori
Immunologi inom det medicinska området Biokemi Molekylärbiologi Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci) Cancer och onkologi
Identifikatorer
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
Anmärkning
QC 20241122
2024-11-202024-11-202025-02-20Bibliografiskt granskad