This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: This data is currently published in PDB data base: and there are no legal or ethical restrictions on sharing our data publicly.įunding: The authors received funding in the form of salary for this work from Shanghai Henlius Biotech, Inc. Received: ApAccepted: SeptemPublished: December 31, 2021Ĭopyright: © 2021 Issafras et al. Balalaeva, Lobachevsky University, RUSSIAN FEDERATION (2021) Structural basis of HLX10 PD-1 receptor recognition, a promising anti-PD-1 antibody clinical candidate for cancer immunotherapy. We compared HLX10 to Nivolumab and Pembrolizumab and it showed similar or better bioactivity in vitro and in vivo, providing a rationale for clinical evaluation in cancer immunotherapy.Ĭitation: Issafras H, Fan S, Tseng C-L, Cheng Y, Lin P, Xiao L, et al. However, HLX10 and Pembrolizumab showed an opposite heavy chain (HC) and light chain (LC) usage, which recognizes several overlapping amino acid residues on PD-1. Notably, HLX10’s epitope was closer to Pembrolizumab’s epitope than Nivolumab’s epitope. Detailed epitope analysis showed that HLX10 has a unique mode of recognition compared to the clinically approved PD1 antibodies Pembrolizumab and Nivolumab. To elucidate HLX10’s mode of action, we solved the structure of HLX10 in complex with PD-1 receptor. The combined inhibition of PD-1/PDL-1 and angiogenesis pathways using anti-VEGF antibody may enhance a sustained suppression of cancer-related angiogenesis and tumor elimination. HLX10, a fully humanized IgG 4 monoclonal antibody against PD-1 receptor, increased functional activities of human T-cells and showed in vitro, and anti-tumor activity in several tumor models. Discovery and development of novel anti PD-1 inhibitors remains a field of intense investigation, where novel monoclonal antibodies (mAbs) and novel antibody formats (e.g., novel isotype, bispecific mAb and low-molecular-weight compounds) are major source of future therapeutic candidates. Cancer immunotherapies, such as checkpoint blockade of programmed cell death protein-1 (PD-1), represents a breakthrough in cancer treatment, resulting in unprecedented results in terms of overall and progression-free survival.
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