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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 Cell proliferation and anti-tumor immunity in mice

Author

Listed:
  • Aman Mebrahtu

    (Biotechnology and Health
    Strike Pharma AB)

  • Ida Laurén

    (Strike Pharma AB
    Uppsala University)

  • Rosanne Veerman

    (Strike Pharma AB)

  • Gözde Güclüler Akpinar

    (Strike Pharma AB)

  • Martin Lord

    (Strike Pharma AB
    Uppsala University)

  • Alexandros Kostakis

    (Strike Pharma AB
    Uppsala University)

  • Juan Astorga-Wells

    (Karolinska Institute)

  • Leif Dahllund

    (Biotechnology and Health
    Drug Discovery and Development)

  • Anders Olsson

    (Biotechnology and Health
    Drug Discovery and Development)

  • Oscar Andersson

    (Biotechnology and Health
    Drug Discovery and Development)

  • Jonathan Persson

    (Biotechnology and Health
    Drug Discovery and Development)

  • Helena Persson

    (Biotechnology and Health
    Drug Discovery and Development)

  • Pierre Dönnes

    (Strike Pharma AB
    SciCross AB)

  • Johan Rockberg

    (Biotechnology and Health
    Strike Pharma AB)

  • Sara Mangsbo

    (Strike Pharma AB
    Uppsala University)

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.

Suggested Citation

  • Aman Mebrahtu & Ida Laurén & Rosanne Veerman & Gözde Güclüler Akpinar & Martin Lord & Alexandros Kostakis & Juan Astorga-Wells & Leif Dahllund & Anders Olsson & Oscar Andersson & Jonathan Persson & He, 2024. "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," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53839-5
    DOI: 10.1038/s41467-024-53839-5
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    References listed on IDEAS

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    1. Luuk Hooren & Alessandra Vaccaro & Mohanraj Ramachandran & Konstantinos Vazaios & Sylwia Libard & Tiarne Walle & Maria Georganaki & Hua Huang & Ilkka Pietilä & Joey Lau & Maria H. Ulvmar & Mikael C. I, 2021. "Agonistic CD40 therapy induces tertiary lymphoid structures but impairs responses to checkpoint blockade in glioma," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    2. Mahesh Yadav & Suchit Jhunjhunwala & Qui T. Phung & Patrick Lupardus & Joshua Tanguay & Stephanie Bumbaca & Christian Franci & Tommy K. Cheung & Jens Fritsche & Toni Weinschenk & Zora Modrusan & Ira M, 2014. "Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing," Nature, Nature, vol. 515(7528), pages 572-576, November.
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