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. 

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Nyckelord

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

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)