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Data from In Vitro Characterization of the Anti-PD-1 Antibody Nivolumab, BMS-936558, and In Vivo Toxicology in Non-Human Primates
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Data from In Vitro Characterization of the Anti-PD-1 Antibody Nivolumab, BMS-936558, and In Vivo Toxicology in Non-Human Primates
Data from In Vitro Characterization of the Anti-PD-1 Antibody Nivolumab, BMS-936558, and In Vivo Toxicology in Non-Human Primates
CW
Changyu Wang
Changyu Wang
KT
Kent B. Thudium
Kent B. Thudium
MH
Minhua Han
Minhua Han
XW
Xi-Tao Wang
Xi-Tao Wang
HH
Haichun Huang
Haichun Huang
DF
Diane Feingersh
Diane Feingersh
CG
Candy Garcia
Candy Garcia
YW
Yi Wu
Yi Wu
MK
Michelle Kuhne
Michelle Kuhne
MS
Mohan Srinivasan
Mohan Srinivasan
SS
Sujata Singh
Sujata Singh
SW
Susan Wong
Susan Wong
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3 April 2023
other
Published by
American Association for Cancer Research (AACR)
https://doi.org/10.1158/2326-6066.c.6548384.v1
Abstract
The programmed death-1 (PD-1) receptor serves as an immunologic checkpoint, limiting bystander tissue damage and preventing the development of autoimmunity during inflammatory responses. PD-1 is expressed by activated T cells and downmodulates T-cell effector functions upon binding to its ligands, PD-L1 and PD-L2, on antigen-presenting cells. In patients with cancer, the expression of PD-1 on tumor-infiltrating lymphocytes and its interaction with the ligands on tumor and immune cells in the tumor microenvironment undermine antitumor immunity and support its rationale for PD-1 blockade in cancer immunotherapy. This report details the development and characterization of nivolumab, a fully human IgG4 (S228P) anti-PD-1 receptor-blocking monoclonal antibody. Nivolumab binds to PD-1 with high affinity and specificity, and effectively inhibits the interaction between PD-1 and its ligands. In vitro assays demonstrated the ability of nivolumab to potently enhance T-cell responses and cytokine production in the mixed lymphocyte reaction and superantigen or cytomegalovirus stimulation assays. No in vitro antibody-dependent cell-mediated or complement-dependent cytotoxicity was observed with the use of nivolumab and activated T cells as targets. Nivolumab treatment did not induce adverse immune-related events when given to cynomolgus macaques at high concentrations, independent of circulating anti-nivolumab antibodies where observed. These data provide a comprehensive preclinical characterization of nivolumab, for which antitumor activity and safety have been demonstrated in human clinical trials in various solid tumors. Cancer Immunol Res; 2(9); 846–56. ©2014 AACR.
Keywords
ANTIBODY
VITRO
NIVOLUMAB ANTIBODIES
ANTI PD
ANTITUMOR
LYMPHOCYTES
ACTIVATED T CELLS
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