An Adaptable Antibody-Based Platform for Flexible Synthetic Peptide Delivery Built on Agonistic CD40 AntibodiesShow others and affiliations
2022 (English)In: Advanced Therapeutics, E-ISSN 2366-3987, Vol. 5, no 7, article id 2200008Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
Wiley , 2022. Vol. 5, no 7, article id 2200008
Keywords [en]
Antibody Drug Affinity Conjugate (ADAC), cancer vaccine, cargo delivery, CD40, immunotherapy, multivalent antibodies, synthetic peptides, antibody conjugate, bispecific antibody, CD40 ligand monoclonal antibody, Fc receptor, immunoglobulin G1, immunoglobulin G2, interleukin 12p40, interleukin 12p70, synthetic peptide, adult, animal cell, animal tissue, antigen binding, antigen presenting cell, Article, binding affinity, CD4+ T lymphocyte, CD8+ T lymphocyte, cell differentiation, cell expansion, controlled study, drug degradation, drug delivery system, drug half life, drug tissue level, embryo, female, genetic drift, high throughput sequencing, human, human cell, in vitro study, in vivo study, internalization (cell), lymphocyte proliferation, male, monocyte, mouse, natural killer cell, nonhuman, pandemic, peripheral blood mononuclear cell, protein stability, T lymphocyte activation, vaccination
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:kth:diva-324571DOI: 10.1002/adtp.202200008ISI: 000810335300001Scopus ID: 2-s2.0-85131734589OAI: oai:DiVA.org:kth-324571DiVA, id: diva2:1742042
Note
QC 20230308
2023-03-082023-03-082023-03-08Bibliographically approved