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

The 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.