Development of a Cytotoxic Antibody-Drug Conjugate Targeting Membrane Immunoglobulin E-Positive Cells.

ABSTRACT: High numbers of membrane immunoglobulin E (IgE)-positive cells are characteristic of allergic conditions, atopic dermatitis, or IgE myeloma. Antibodies targeting the extracellular membrane-proximal domain of the membranous IgE-B-cell receptor (BCR) fragment can be used for specific depletion of IgE-BCR-positive cells. In this study, we derivatized such an antibody with a toxin and developed an antibody-drug conjugate (ADC) that showed strong cytotoxicity for an IgE-positive target cell line. Site-specific conjugation with maleimidocaproyl-valine-citrulline-p-aminobenzoyloxycarbonyl-monomethyl-auristatin E via a newly introduced single cysteine residue was used to prepare a compound with a drug-antibody ratio of 2 and favorable biophysical properties. The antibody was rapidly taken u

SUBMITTER: Rodak A 

PROVIDER: S-EPMC10573690 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature