Stephen S. Yoo, Ezra M. Chung, Yong-Soo KIm, Mien-Chie Hung, Chia-Wei Li, and Seung-Oe Lim
- STCUBE, Inc., Seoul (KR);
- BOARD OF REGENTS, THE UNIVERSITY OF TEXAS, Austin, TX (US)
Antibodies that bind specifically to glycosylated PD-L1 relative to unglycosylated PD-L1 are provided. Antibodies that recognize specific epitopes of glycosylated PD-L1 protein and can block the binding of PD-L1 to PD-1 are provided. In some aspects, PD-L1 polypeptides comprising glycosylated amino acid residues at amino and carboxy terminal positions of the PD-L1 extracellular domain are also provided. Methods for making and using such antibodies and polypeptides (e.g., for the treatment of cancer) are also provided.
CovalX Technology Used
Mouse monoclonal anti-glycPD-L1 antibody STM004 was epitope mapped using the CovalX epitope mapping service. It was investigated whether or not unstructured peptides generated by proteolysis of the PD-L1 antigen could inhibit the inteitope-mapping-hdx-ms/raction between PD-L1 protein as a target antigen and the anti-glycPD-L1 antibodies. From the epitope mapping, it was also determined that anti-PD-L1 MAb STM004 recognizes an epitope on PD-L1 that is conformational. Specifically, it was found that STM004 binds to an epitope on PD-L1 that is in contact with the amino acid residues at Y56, K62 and K75 contained within residues 48 to 78. STM115 binds to an epitope on PD-L1 that is in contact with the amino acid residues at K62, H69 and K75 contained within the residues 61 to 78.