Programmed cell death protein 1

PD-1programmed cell death 1CD279PD1PDCD1Anti-PD-1Anti-PD-1 drugsPCDP1PDPD-1 protein
Programmed cell death protein 1, also known as PD-1 and CD279 (cluster of differentiation 279), is a protein on the surface of cells that has a role in regulating the immune system's response to the cells of the human body by down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity.wikipedia
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Immune checkpoint

inhibition of negative immune regulationcheckpointcheckpoint inhibitor
PD-1 is an immune checkpoint and guards against autoimmunity through two mechanisms.
Currently approved checkpoint inhibitors block CTLA4 and PD-1 and PD-L1.

Tasuku Honjo

In a screen for genes involved in apoptosis, Yasumasa Ishida, Tasuku Honjo and colleagues at Kyoto University in 1992 discovered and named PD-1.
He shared the 2018 Nobel Prize in Medicine or Physiology and is best known for his identification of programmed cell death protein 1 (PD-1).

PD-L1

CD274PD-1 ligand 1programmed death-ligand 1
PD-1 binds two ligands, PD-L1 and PD-L2. PD-1 has two ligands, PD-L1 and PD-L2, which are members of the B7 family.
The binding of PD-L1 to the inhibitory checkpoint molecule PD-1 transmits an inhibitory signal based on interaction with phosphatases (SHP-1 or SHP-2) via Immunoreceptor Tyrosine-Based Switch Motif (ITSM) motif.

Immunoglobulin superfamily

Immunoglobulin (Ig) superfamilyimmunoglobulinIg
PD-1 is a cell surface receptor that belongs to the immunoglobulin superfamily and is expressed on T cells and pro-B cells.

T cell

T cellsT-cellT-cells
PD-1 is a cell surface receptor that belongs to the immunoglobulin superfamily and is expressed on T cells and pro-B cells. Programmed cell death protein 1, also known as PD-1 and CD279 (cluster of differentiation 279), is a protein on the surface of cells that has a role in regulating the immune system's response to the cells of the human body by down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity.
Another factor able to induce exhaustion are inhibitory receptors including programmed cell death protein 1 (PD1), CTLA-4, T cell membrane protein-3 (TIM3), and lymphocyte activation gene 3 protein (LAG3).

Lipopolysaccharide

endotoxinLPSlipopolysaccharides
PD-L1 protein is upregulated on macrophages and dendritic cells (DC) in response to LPS and GM-CSF treatment, and on T cells and B cells upon TCR and B cell receptor signaling, whereas in resting mice, PD-L1 mRNA can be detected in the heart, lung, thymus, spleen, and kidney.
Said et al. showed that LPS causes an IL-10-dependent inhibition of CD4 T-cell expansion and function by up-regulating PD-1 levels on monocytes which leads to IL-10 production by monocytes after binding of PD-1 by PD-L1.

Pembrolizumab

KeytrudaKeytruda (Merck/MSD)Keytruda (pembrolizumab)
Pembrolizumab (Keytruda, MK-3475, Merck), which also targets PD-1 receptors, was approved by the FDA in Sept 2014 to treat metastatic melanoma.
It targets the programmed cell death protein 1 (PD-1) receptor of lymphocytes.

B7 (protein)

B7B7 family
PD-1 has two ligands, PD-L1 and PD-L2, which are members of the B7 family.

Checkpoint inhibitor

Checkpoint inhibitioncheckpoint inhibitorscheckpoint inhibitor therapy
Combination therapy using both anti-PD1 along with anti-CTLA4 therapeutics have emerged as important tumor treatments within the field of checkpoint inhibition. Other drugs in early stage development targeting PD-1 receptors (checkpoint inhibitors) are Pidilizumab (CT-011, Cure Tech) and BMS-936559 (Bristol Myers Squibb).
Currently approved checkpoint inhibitors target the molecules CTLA4, PD-1, and PD-L1.

Bristol-Myers Squibb

Bristol-MyersBristol Myers SquibbSquibb
One such anti-PD-1 antibody drug, nivolumab, (Opdivo - Bristol-Myers Squibb), produced complete or partial responses in non-small-cell lung cancer, melanoma, and renal-cell cancer, in a clinical trial with a total of 296 patients.
In December 2014 the company received FDA approval for the use of the PD-1 inhibitor nivolumab (Opdivo) in treating patients whose skin cancer cannot be removed or have not responded to previous drug therapies.

Pidilizumab

Other drugs in early stage development targeting PD-1 receptors (checkpoint inhibitors) are Pidilizumab (CT-011, Cure Tech) and BMS-936559 (Bristol Myers Squibb).
Pidilizumab was originally thought to bind to the PD-1 immune checkpoint molecule, however, recent evidence suggests that Delta-like 1 (DLL1) is its primary binding target while binding to PD-1 is secondary and restricted to non-glycosylated and hypoglycosylated forms of this molecule.

Nivolumab

Opdivo
One such anti-PD-1 antibody drug, nivolumab, (Opdivo - Bristol-Myers Squibb), produced complete or partial responses in non-small-cell lung cancer, melanoma, and renal-cell cancer, in a clinical trial with a total of 296 patients. Most recently, the FDA has approved a combination therapy with both anti-CTLA4 (ipilimumab) and anti-PD1 (nivolumab) in October 2015. Nivolumab (Opdivo, Bristol-Myers Squibb) was approved in Japan in July 2014 and by the US FDA in December 2014 to treat metastatic melanoma.
Nivolumab is a fully human monoclonal immunoglobulin G4 antibody to PD-1.

Melanoma

malignant melanomametastatic melanomamelanomas
Pembrolizumab (Keytruda, MK-3475, Merck), which also targets PD-1 receptors, was approved by the FDA in Sept 2014 to treat metastatic melanoma. Nivolumab (Opdivo, Bristol-Myers Squibb) was approved in Japan in July 2014 and by the US FDA in December 2014 to treat metastatic melanoma.
Immune check point inhibitors include anti-CTLA-4 monoclonal antibodies (ipilimumab and tremelimumab), toll-like receptor (TLR) agonists, CD40 agonists, anti-PD-1 (pembrolizumab, pidilizumab, and nivolumab) and PD-L1 antibodies.

Atezolizumab

TecentriqMPDL3280A
Both Atezolizumab (MPDL3280A, Roche) and Avelumab (Merck KGaA, Darmstadt, Germany & Pfizer) target the similar PD-L1 receptor.
Atezolizumab blocks the interaction of PD-L1 with programmed cell death protein 1 (PD-1) and CD80 receptors (B7-1Rs).

Avelumab

Bavencio
Both Atezolizumab (MPDL3280A, Roche) and Avelumab (Merck KGaA, Darmstadt, Germany & Pfizer) target the similar PD-L1 receptor.
Avelumab is a whole monoclonal antibody of isotype IgG1 that binds to the programmed death-ligand 1 (PD-L1) and therefore inhibits binding to its receptor programmed cell death 1 (PD-1).

TIGIT

Drugs targeting PD-1 in combination with other negative immune checkpoint receptors, such as (TIGIT), may augment immune responses and/or facilitate HIV eradication.
Elevated TIGIT levels remained sustained even among those with undetectable viral loads and a large fraction of HIV-specific CD8+ T cells simultaneously express both TIGIT and another negative checkpoint receptor, Programmed Death Protein 1 (PD-1) and retained several features of exhausted T cells.

Cluster of differentiation

CDC'''luster of '''D'''ifferentiationclusters of differentiation
Programmed cell death protein 1, also known as PD-1 and CD279 (cluster of differentiation 279), is a protein on the surface of cells that has a role in regulating the immune system's response to the cells of the human body by down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity.

Cell surface receptor

transmembrane receptorreceptorcell surface receptors
Programmed cell death protein 1, also known as PD-1 and CD279 (cluster of differentiation 279), is a protein on the surface of cells that has a role in regulating the immune system's response to the cells of the human body by down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity.

Immune system

immuneimmune responseimmune function
Programmed cell death protein 1, also known as PD-1 and CD279 (cluster of differentiation 279), is a protein on the surface of cells that has a role in regulating the immune system's response to the cells of the human body by down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity.

Apoptosis

apoptoticprogrammed cell deathcell death
In a screen for genes involved in apoptosis, Yasumasa Ishida, Tasuku Honjo and colleagues at Kyoto University in 1992 discovered and named PD-1. First, it promotes apoptosis (programmed cell death) of antigen-specific T-cells in lymph nodes.

Antigen

antigensantigenicantigenic proteins
First, it promotes apoptosis (programmed cell death) of antigen-specific T-cells in lymph nodes.

Lymph node

lymph glandslymph nodesfollicles
First, it promotes apoptosis (programmed cell death) of antigen-specific T-cells in lymph nodes.

Regulatory T cell

regulatory T cellsTregTregs
Second, it reduces apoptosis in regulatory T cells (anti-inflammatory, suppressive T cells).

Protein

proteinsproteinaceousstructural proteins
The PD-1 protein in humans is encoded by the PDCD1 gene.

Gene

genesnumber of genesgene sequence
The PD-1 protein in humans is encoded by the PDCD1 gene.