TY - JOUR
T1 - Clinical Pharmacology and Interplay of Immune Checkpoint Agents
T2 - A Yin-Yang Balance
AU - Geraud, Arthur
AU - Gougis, Paul
AU - Vozy, Aurore
AU - Anquetil, Celine
AU - Allenbach, Yves
AU - Romano, Emanuela
AU - Funck-Brentano, Elisa
AU - Moslehi, Javid J.
AU - Johnson, Douglas B.
AU - Salem, Joe Elie
N1 - Publisher Copyright:
© 2021 by Annual Reviews. All rights reserved.
PY - 2021/1/6
Y1 - 2021/1/6
N2 - T cells have a central role in immune system balance. When activated, they may lead to autoimmune diseases. When too anergic, they contribute to infection spread and cancer proliferation. Immune checkpoint proteins regulate T cell function, including cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) and its ligand (PD-L1). These nodes of self-tolerance may be exploited pharmacologically to downregulate (CTLA-4 agonists) and activate CTLA-4 and PD-1/PD-L1 antagonists, also called immune checkpoint inhibitors (ICIs) the immune system.CTLA-4 agonists are used to treat rheumatologic immune disorders and graft rejection. CTLA-4, PD-1, and PD-L1 antagonists are approved for multiple cancer types and are being investigated for chronic viral infections. Notably, ICIs may be associated with immune-related adverse events (irAEs), which can be highly morbid or fatal. CTLA-4 agonism has been a promising method to reverse such life-threatening irAEs. Herein, we review the clinical pharmacology of these immune checkpoint agents with a focus on their interplay in human diseases.
AB - T cells have a central role in immune system balance. When activated, they may lead to autoimmune diseases. When too anergic, they contribute to infection spread and cancer proliferation. Immune checkpoint proteins regulate T cell function, including cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) and its ligand (PD-L1). These nodes of self-tolerance may be exploited pharmacologically to downregulate (CTLA-4 agonists) and activate CTLA-4 and PD-1/PD-L1 antagonists, also called immune checkpoint inhibitors (ICIs) the immune system.CTLA-4 agonists are used to treat rheumatologic immune disorders and graft rejection. CTLA-4, PD-1, and PD-L1 antagonists are approved for multiple cancer types and are being investigated for chronic viral infections. Notably, ICIs may be associated with immune-related adverse events (irAEs), which can be highly morbid or fatal. CTLA-4 agonism has been a promising method to reverse such life-threatening irAEs. Herein, we review the clinical pharmacology of these immune checkpoint agents with a focus on their interplay in human diseases.
KW - Immune checkpoint inhibitors
KW - cancer
KW - immune checkpoint agents
KW - immune-related adverse events
KW - pharmacokinetic
KW - pharmacology
UR - http://www.scopus.com/inward/record.url?scp=85092554716&partnerID=8YFLogxK
U2 - 10.1146/annurev-pharmtox-022820-093805
DO - 10.1146/annurev-pharmtox-022820-093805
M3 - Review article
C2 - 32871087
AN - SCOPUS:85092554716
SN - 0362-1642
VL - 61
SP - 85
EP - 112
JO - Annual Review of Pharmacology and Toxicology
JF - Annual Review of Pharmacology and Toxicology
ER -