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

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Nov 5

PMID 39500897

Authors

Aman Mebrahtu

Ida Lauren

Rosanne Veerman

Gozde Gucluler Akpinar

Martin Lord

Alexandros Kostakis

Juan Astorga-Wells

Leif Dahllund

Anders Olsson

Oscar Andersson

Jonathan Persson

Helena Persson

Pierre Donnes

Johan Rockberg

Sara Mangsbo

Affiliations

Soon will be listed here.

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.

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