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Preclinical comparison of prolgolimab, pembrolizumab and nivolumab

Prolgolimab is a recombinant IgG1-based anti-PD-1 antibody, whose properties were improved by the introduction of the LALA mutation, and which has demonstrated high efficacy in patients with metastatic melanoma. This paper presents the results of comparative preclinical studies of antigen-binding an...

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Published in:	Scientific reports 2024-10, Vol.14 (1), p.23136-13, Article 23136
Main Authors:	Gordeev, Aleksandr, Vaal, Andrei, Puchkova, Maria, Smirnova, Iana, Doronin, Aleksandr, Znobishcheva, Anna, Zhmudanova, Daria, Aleksandrov, Aleksei, Sukchev, Mikhail, Imyanitov, Evgeny, Solovyev, Valery, Iakovlev, Pavel
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Language:	English
Subjects:	631/67/1059/153 631/67/1059/2325 Amino acids Animals Antibodies Antibodies, Monoclonal, Humanized - pharmacology Antibodies, Monoclonal, Humanized - therapeutic use Antibody-Dependent Cell Cytotoxicity - drug effects Antigens Antineoplastic Agents, Immunological - pharmacology Antineoplastic Agents, Immunological - therapeutic use Cell activation Cell Line, Tumor Cytotoxicity Female Humanities and Social Sciences Humans Immune system Immunoglobulin G Ligands Lymphocytes T Melanoma Melanoma - drug therapy Melanoma - immunology Melanoma - pathology Metastases Mice multidisciplinary Mutation Nivolumab - pharmacology Nivolumab - therapeutic use PD-1 protein Pembrolizumab Phagocytosis Programmed Cell Death 1 Receptor - antagonists & inhibitors Programmed Cell Death 1 Receptor - immunology Science Science (multidisciplinary)
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description	Prolgolimab is a recombinant IgG1-based anti-PD-1 antibody, whose properties were improved by the introduction of the LALA mutation, and which has demonstrated high efficacy in patients with metastatic melanoma. This paper presents the results of comparative preclinical studies of antigen-binding and effector functions involving prolgolimab and conventional IgG4 antibodies, nivolumab and pembrolizumab. None of the studied antibodies had undesirable antibody-dependent cellular cytotoxicity activity. Prolgolimab has shown higher PD-1 receptor occupancy and T-cell activation, but lower propensity to activate antibody-dependent cellular phagocytosis as compared to nivolumab and pembrolizumab. An in vivo study in mice inoculated with CT26.wt cancer cells showed that tumor growth inhibition was 16% for pembrolizumab and 56% for prolgolimab. This study warrants clinical comparison of IgG1- and IgG4-based anti-PD-1 antibodies.
doi_str_mv	10.1038/s41598-024-72118-3
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subjects	631/67/1059/153 631/67/1059/2325 Amino acids Animals Antibodies Antibodies, Monoclonal, Humanized - pharmacology Antibodies, Monoclonal, Humanized - therapeutic use Antibody-Dependent Cell Cytotoxicity - drug effects Antigens Antineoplastic Agents, Immunological - pharmacology Antineoplastic Agents, Immunological - therapeutic use Cell activation Cell Line, Tumor Cytotoxicity Female Humanities and Social Sciences Humans Immune system Immunoglobulin G Ligands Lymphocytes T Melanoma Melanoma - drug therapy Melanoma - immunology Melanoma - pathology Metastases Mice multidisciplinary Mutation Nivolumab - pharmacology Nivolumab - therapeutic use PD-1 protein Pembrolizumab Phagocytosis Programmed Cell Death 1 Receptor - antagonists & inhibitors Programmed Cell Death 1 Receptor - immunology Science Science (multidisciplinary)
title	Preclinical comparison of prolgolimab, pembrolizumab and nivolumab
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