Clinical Pharmacology and Interplay of Immune Checkpoint Agents: A Yin-Yang Balance

被引:65
作者
Geraud, Arthur [1 ,2 ,3 ]
Gougis, Paul [1 ,2 ]
Vozy, Aurore [1 ,2 ]
Anquetil, Celine [4 ]
Allenbach, Yves [4 ]
Romano, Emanuela [5 ]
Funck-Brentano, Elisa [6 ]
Moslehi, Javid J. [7 ]
Johnson, Douglas B. [7 ]
Salem, Joe-Elie [1 ,2 ,7 ]
机构
[1] Sorbonne Univ, INSERM, UNICO GRECO Cardiooncol Program, CLIP2 Galilee,CIC Paris Est 1901, F-75013 Paris, France
[2] Hop La Pitie Salpetriere, AP HP, Dept Pharmacol, F-75013 Paris, France
[3] Gustave Roussy, Dept Drug Dev DITEP, F-94805 Villejuif, France
[4] Sorbonne Univ, AP HP, INSERM, Dept Internal Med, F-75013 Paris, France
[5] Inst Curie, INSERM, U932, Ctr Canc Immunotherapy, F-75248 Paris 05, France
[6] Univ Paris Saclay, Ambroise Pare Hosp, AP HP, Dept Gen & Oncol Dermatol,EA 4340, F-92100 Boulogne, France
[7] Vanderbilt Univ, Med Ctr, Dept Med, Cardiooncol Program, Nashville, TN 37232 USA
来源
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 61, 2021 | 2021年 / 61卷
关键词
immune checkpoint inhibitors; immune checkpoint agents; pharmacology; pharmacokinetic; immune-related adverse events; cancer; NIVOLUMAB PLUS IPILIMUMAB; T-CELL-ACTIVATION; RHEUMATOID-ARTHRITIS; ANTI-PD-L1; ANTIBODY; FC-RECEPTOR; FULMINANT MYOCARDITIS; BELATACEPT EXPOSURE; ADVERSE EVENTS; FUSION PROTEIN; EMERGING ROLE;
D O I
10.1146/annurev-pharmtox-022820-093805
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:85 / 112
页数:28
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