Structural Insights into the ADCC Mechanism and Resistance of Mogamulizumab, a First-in-Class Anti-CCR4 Therapy for Cutaneous T Cell Lymphoma.

ABSTRACT: Mogamulizumab is a humanized monoclonal antibody that targets C-C chemokine receptor 4 (CCR4) present on certain T cells in lymphomas and leukemias. This antibody-based therapy has demonstrated efficacy in treating various cutaneous T cell lymphomas (CTCLs), including mycosis fungoides and Sézary syndrome, through the depletion of CCR4-expressing T cells by antibody-dependent cellular cytotoxicity (ADCC). However, the precise epitope and binding mode of mogamulizumab responsible for its augmented ADCC activity remain undisclosed. Here, X-ray crystallographic studies of mogamulizumab in complex with a 28-residue N-terminal peptide indicated that SIYSNYYLYES (residues 14-24) would constitute the antibody epitope. Another high-resolution structure, using a short core peptide of these 11 resid

SUBMITTER: Choi SB 

PROVIDER: S-EPMC12193575 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature