2024-11-12 スウェーデン王立工科大学(KTH)
<関連情報>
- https://www.kth.se/en/om/nyheter/centrala-nyheter/new-immunotherapy-suggests-quicker-more-affordable-individualized-treatment-1.1369334
- https://www.nature.com/articles/s41467-024-53839-5
抗体-ペプチドコンジュゲート形成が可能な二重特異性CD40作動性抗体により、がん特異的ペプチド送達が可能となり、マウスにおけるT細胞増殖と抗腫瘍免疫の改善がもたらされた A bispecific CD40 agonistic antibody allowing for antibody-peptide conjugate formation to enable cancer-specific peptide delivery, resulting in improved T Cell proliferation and anti-tumor immunity in mice
Aman Mebrahtu,Ida Laurén,Rosanne Veerman,Gözde Güclüler Akpinar,Martin Lord,Alexandros Kostakis,Juan Astorga-Wells,Leif Dahllund,Anders Olsson,Oscar Andersson,Jonathan Persson,Helena Persson,Pierre Dönnes,Johan Rockberg & Sara Mangsbo
Nature Communications Published:05 November 2024
DOI:https://doi.org/10.1038/s41467-024-53839-5
Abstract
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.
