An Adaptable Antibody‐Based Platform for Flexible Synthetic Peptide Delivery Built on Agonistic CD40 Antibodies

Abstract

AbstractThe agonistic potentials of therapeutic anti‐CD40 antibodies have been profiled in relation to antibody isotype and epitope specificity. 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 (APCs) 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. Herein, a bispecific antibody targeting CD40 as a means to deliver cargo (i.e., synthetic peptides) into APCs through a non‐covalent, high‐affinity interaction between the antibody and the cargo peptide, further referred to as the Adaptable Drug Affinity Conjugate (ADAC) technology, has been developed. The ADAC platform demonstrated a target‐specific CD4+ and CD8+ T cell expansion in vitro and significantly improved peptide‐specific CD8+ T cell proliferation in vivo. In addition, the strategy dramatically improved the in vitro and in vivo half‐life of the synthetic peptides. 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‐shelf product, and the peptide antigen is synthesized based on next‐generation sequencing data mining.