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Drug Discovery Seminars: An adaptable Drug Affinity Conjugate (ADAC) targeting CD40

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Drug Discovery Seminars: An adaptable Drug Affinity Conjugate (ADAC) targeting CD40

Virtual Event Virtual Event

June 4 @ 13:00 13:45 CEST

Proof of Concept and Pharmaceutical profiling

Sara Mangsbo, Uppsala University

Abstract:

Much attention has focused on developing CD40 directed agonistic monoclonal antibody therapy. Monoclonal antibodies targeting CD40 have been profiled for their epitope specificity and isotype in relation to their agonistic potential. Still, clinical impact relies on a well-balanced clinical efficacy versus target-mediated toxicity. As CD40-mediated immune activation must rely on a combination of stimulation of antigen-presenting cells alongside antigen-presentation, for efficient T cell priming, alternative approaches to improve the therapeutic outcome of CD40-targeting strategies should focus on providing optimal antigen presentation together with CD40 stimulation. We have developed a bispecific antibody targeting CD40 as a means to carry in cargo (herein synthetic peptides) into antigen-presenting cells through a non-covalent, high-affinity interaction between the antibody and the cargo peptide, further referred to as the Antibody Drug Affinity Conjugate (ADAC) technology. The ADAC can improve both CD4+ and CD8+ T cell expansion in vitro and significantly improve CD8+ T cell proliferation in vivo. In addition, the strategy leads to a stabilization of the half-life of the synthetic peptide. Future applications of ADAC involve pandemic preparedness to viral genetic drift as well as neoepitope vaccination strategies where the bispecific antibody is an off-the-shelve product, and the peptide antigen is synthesized based on next-generation sequencing data mining. 

A short speaker biography:

Sara Mangsbo (PhD) is Associate senior lecturer in antibody drugs and Associate professor in Experimental clinical immunology at Uppsala University. Dr Mangsbo earned her PhD in 2010 in cancer immunotherapy at Uppsala University and has since then focused her research on antibody-based drug delivery and synthetic long peptides and was recently awarded the SITC team award within the SLP stream. She is a serial entrepreneur and has founded Immuneed AB, a service provider of immunotoxicity measurements in human whole blood. She is the Chief Development Officer of Ultimovacs and the co-founder of Vivologica AB and STRIKE pharma AB.  She drives a translational research project with the ambition and track-record of taking research projects into clinical trial testing.