Abstract B113: In vivo characterization of anti-PD-1 antibody REGN2810 in human PD-1 knock-in mice
| Autor: | Dimitris Skokos, Janelle C. Waite, Venus Lai, Drew Murphy, Elena Burova, William Poueymirou, Nicholas J. Papadopoulos, Gavin Thurston, Israel Lowy, Ella Ioffe, Omaira Allbritton |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research biology business.industry medicine.medical_treatment Immunology 03 medical and health sciences 030104 developmental biology Immune system Cancer immunotherapy In vivo Monoclonal Cancer cell medicine biology.protein Cancer research Cytotoxic T cell Antibody Antigen-presenting cell business |
| Zdroj: | Cancer Immunology Research. 4:B113-B113 |
| ISSN: | 2326-6074 2326-6066 |
| Popis: | The Programmed Death-1 (PD-1) receptor is an immunologic inhibitory checkpoint, expressed by activated T cells. PD-1 signals upon binding to its ligands PD-L1 and PD-L2 expressed on antigen presenting cells and some types of cancer cells, and delivers inhibitory signals to T cells, resulting in suppression of T-cell effector function. In cancer patients, PD-1 is expressed on tumor-infiltrating lymphocytes and inhibits antitumor immune responses through ligand binding. Clinically, it has been shown that antibodies (Abs) that block the interaction between PD-1 and PD-L1 can release the cytotoxic function of tumor-specific T cells, yielding durable objective responses in multiple cancer types. This study describes preclinical characterization of REGN2810, a fully human hinge-stabilized IgG4 monoclonal Ab that binds to the extracellular domain of human PD-1 with high affinity and specificity and inhibits interaction of PD-1 with its ligands. Taking advantage of the ability of human PD-1 to interact with murine PD-L1, we generated a mouse with human PD-1 gene knock-in allowing direct testing of our anti-human PD-1 Ab. Human PD-1 knock-in mice express a hybrid protein containing the extracellular portion of human PD-1, and transmembrane and intracellular domains of mouse PD-1. We demonstrated functional PD-1/PD-L1 signaling and immune responses in this model, and confirmed REGN2810 binding to hybrid PD-1 receptor on mouse T cells in vivo following REGN2810 injections. Prophylactic and therapeutic treatments of subcutaneous syngeneic tumors with REGN2810 in human PD-1 knock-in mice resulted in a dose-dependent suppression of tumor growth. Currently REGN2810 anti-PD-1 Ab is in phase 1 clinical trials for oncology indications. Citation Format: Elena Burova, Omaira Allbritton, William Poueymirou, Venus Lai, Janelle Waite, Dimitris Skokos, Nicholas Papadopoulos, Drew Murphy, Israel Lowy, Ella Ioffe, Gavin Thurston. In vivo characterization of anti-PD-1 antibody REGN2810 in human PD-1 knock-in mice. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B113. |
| Databáze: | OpenAIRE |
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