Poster Presentations
Day 2, June 11（Thu.） Room P (5F 501+502)
- 2P-41
Evaluation of Novel Ligand Loading in LYTAC-Related Antibody Conjugates Using Benchtop MALDI-TOF MS
(1Shimadzu, 2Natl. Inst. Health Sci.)
oTakashi Nishikaze1, Takahito Ito2, Nobumichi Ohoka2, Michihiko Aoyama2, Takashi Misawa2, Takao Inoue2, Akiko Ishii-watanabe2, Yosuke Demizu2
Asialoglycoprotein receptor (ASGPR)-mediated drug delivery systems are widely used for liver targeting, and triantennary N-acetylgalactosamine (Tri-GalNAc) ligands exhibit high affinity for trimeric ASGPR. Although Tri-GalNAc has been successfully applied to oligonucleotide therapeutics, its flexible linker structure is considered suboptimal for multivalent receptor binding. To address this limitation, a novel ligand was designed in which three GalNAc units are strategically positioned on a helical peptide scaffold, resulting in enhanced cellular uptake efficiency and liver selectivity. Recently, GalNAc ligands have also been applied to lysosome targeting chimeras (LYTACs) by conjugation to antibodies. In this study, cetuximab was modified with the newly designed helical peptide ligand having three GalNAc residues to generate LYTAC related antibody conjugates. The number of ligand loading was evaluated using a benchtop MALDI-TOF mass spectrometer after enzymatic deglycosylation. Signals corresponding to antibody heavy and light chains were clearly observed, enabling estimation of ligand loading numbers. These results demonstrate that benchtop MALDI-TOF MS provides a simple and effective approach for characterizing ligand loading in LYTAC-related antibody conjugates.