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 () and Sara Mangsbo ()
Additional contact information
Aman Mebrahtu: Biotechnology and Health
Ida Laurén: Strike Pharma AB
Rosanne Veerman: Strike Pharma AB
Gözde Güclüler Akpinar: Strike Pharma AB
Martin Lord: Strike Pharma AB
Alexandros Kostakis: Strike Pharma AB
Juan Astorga-Wells: Karolinska Institute
Leif Dahllund: Biotechnology and Health
Anders Olsson: Biotechnology and Health
Oscar Andersson: Biotechnology and Health
Jonathan Persson: Biotechnology and Health
Helena Persson: Biotechnology and Health
Pierre Dönnes: Strike Pharma AB
Johan Rockberg: Biotechnology and Health
Sara Mangsbo: Strike Pharma AB

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-53839-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53839-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-53839-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().