PD-L1

Synonyms

Programmed Cell Death 1 Ligand 1, PDCD1L1, B7H1, PDL1, Programmed Death Ligand 1, B7-H1, B7-H, B7-H1 Antigen, CD274, B7 homolog 1, PDCD1 ligand 1, PD-L1, PDCD1LG1, CD274 Molecule, CD274 Antigen, HPD-L1

Description

Programmed death-ligand 1 is a protein that in humans is encoded by the CD274 gene.Programmed death-ligand 1 (PD-L1) is a 40kDa type 1 transmembrane protein that has been speculated to play a major role in suppressing the adaptive arm of immune system during particular events such as pregnancy, tissue allografts, autoimmune disease and other disease states such as hepatitis. Normally the adaptive immune system reacts to antigens that are associated with immune system activation by exogenous or endogenous danger signals. In turn, clonal expansion of antigen-specific CD8+ T cells and/or CD4+ helper cells is propagated. 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).It plays a critical role in induction and maintenance of immune tolerance to self . As a ligand for the inhibitory receptor PDCD1/PD-1, modulates the activation threshold of T-cells and limits T-cell effector response . Through a yet unknown activating receptor, may costimulate T-cell subsets that predominantly produce interleukin-10 (IL10) .The PDCD1-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and escape destruction by the immune system, thereby facilitating tumor survival . The interaction with PDCD1/PD-1 inhibits cytotoxic T lymphocytes (CTLs) effector function. The blockage of the PDCD1-mediated pathway results in the reversal of the exhausted T-cell phenotype and the normalization of the anti-tumor response, providing a rationale for cancer immunotherapy.

KO Status

Immunization

Drug Information

Launched drugs: 3
Drugs in clinical trials: 59
Latest Research Phase: Approved

Drug Name

Code

Phase

Company

Indications

Clinical Trials

Avelumab

PF-06834635, MSB-0010718C

Approved

Merck Serono

Ovarian Neoplasms, Solid tumours, Carcinoma, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Merkel Cell, Carcinoma, Renal Cell, Stomach Neoplasms, Hodgkin Disease, Carcinoma, Transitional Cell, Pancreatic Neoplasms, Triple Negative Breast Neoplasms, Glioblastoma, Carcinoma, Ovarian Epithelial, Papillomavirus Infections, Lymphoma, Large B-Cell, Diffuse, Chordoma, Breast Neoplasms, Prostatic Neoplasms, Colorectal Neoplasms, Peritoneal Neoplasms, Esophageal Squamous Cell Carcinoma, Lymphoma, Non-Hodgkin, Lymphoma, Fallopian Tube Neoplasms, Carcinoma, Non-Small-Cell Lung, Leukemia, Lymphocytic, Chronic, B-Cell, Melanoma, Carcinoma, Hepatocellular, Uterine Cervical Neoplasms

Carrizumab

Atezolizumab

RG-7446, MPDL-3280A, RO-5541267, 52CMI0WC3Y (UNII code)

Approved

Genentech Inc

Solid tumours, Hematologic Neoplasms, Head and Neck Neoplasms, Ovarian Neoplasms, Liver Neoplasms, Kidney Neoplasms, Carcinoma, Renal Cell, Squamous Cell Carcinoma of Head and Neck, Esophageal Neoplasms, Stomach Neoplasms, Carcinoma, Merkel Cell, Small Cell Lung Carcinoma, Triple Negative Breast Neoplasms, Carcinoma, Transitional Cell, Pancreatic Neoplasms, Papillomavirus Infections, Kidney Diseases, Prostatic Neoplasms, Castration-Resistant, Urinary Bladder Neoplasms, Sarcoma, Synovial, Liposarcoma, Urologic Diseases, Urethral Neoplasms, Breast Neoplasms, Sarcoma, Microsatellite Instability, Prostatic Neoplasms, Cholangiocarcinoma, Colorectal Neoplasms, Genital Neoplasms, Female, Urologic Neoplasms, Peritoneal Neoplasms, Bile Duct Neoplasms, Metastatic breast cancer, Esophageal Squamous Cell Carcinoma, Lymphoma, Non-Hodgkin, Lung Neoplasms, Thymoma, Lymphoma, Carcinoma, Squamous Cell, Neoplasms, Unknown Primary, Uterine Neoplasms, Leukemia, Myeloid, Acute, Gallbladder Neoplasms, Fallopian Tube Neoplasms, Urogenital Neoplasms, Carcinoma, Non-Small-Cell Lung, Carcinoma, Hepatocellular, Melanoma, Uterine Cervical Neoplasms, Leukemia, Lymphocytic, Chronic, B-Cell, Neoplasm Metastasis, Liposarcoma, Myxoid, Adenocarcinoma

Durvalumab

28X28X9-OKV (UNII code), MEDI-4736

Approved

Medimmune Llc

Head and Neck Neoplasms, Ovarian Neoplasms, Solid tumours, Kidney Neoplasms, Biliary Tract Neoplasms, Hematologic Neoplasms, Carcinoma, Renal Cell, Carcinoma, Squamous Cell Carcinoma of Head and Neck, Esophageal Neoplasms, Stomach Neoplasms, Carcinoma, Transitional Cell, Pancreatic Neoplasms, Triple Negative Breast Neoplasms, Small Cell Lung Carcinoma, Papillomavirus Infections, Lymphoma, Large B-Cell, Diffuse, Multiple Myeloma, Urinary Bladder Neoplasms, Prostatic Neoplasms, Castration-Resistant, Digestive System Neoplasms, Prostatic Neoplasms, Breast Neoplasms, Colorectal Neoplasms, Peritoneal Neoplasms, Lymphoma, T-Cell, Cutaneous, Lung Neoplasms, Esophageal Squamous Cell Carcinoma, Carcinoma, Pancreatic Ductal, Fallopian Tube Neoplasms, Carcinoma, Squamous Cell, Lymphoma, Lymphoma, Non-Hodgkin, Carcinoma, Non-Small-Cell Lung, Uterine Cervical Neoplasms, Melanoma, Carcinoma, Hepatocellular, Carcinoma, Endometrioid

JS-003

JS-003

Shanghai Junshi Biosciences Co Ltd

Solid tumours

Envafolimab

KN-035, KN035, ASC22, ASC-22

NDA/BLA

Suzhou Alphamab Co Ltd

Shock, Septic, Solid tumours, Biliary Tract Neoplasms, Hepatitis B, Chronic, Esophageal Neoplasms, Stomach Neoplasms, Sepsis, Dermatofibrosarcoma, Hepatitis B, Sarcoma, Bile Duct Neoplasms, Colorectal Neoplasms, Carcinoma, Hepatocellular

IBI-322

IBI-322, IBI322

NDA/BLA

Innovent Biologics(Suzhou) Co Ltd

Hematologic Neoplasms, Solid tumours, Carcinoma, Transitional Cell, Neoplasms

Recombinant human anti-PDL1 monoclonal antibody (CStone Pharmaceuticals)

WBP-3155, CS-1001

NDA/BLA

Cstone Pharmaceuticals (Suzhou) Co Ltd

Ovarian Neoplasms, Solid tumours, Head and Neck Neoplasms, Esophageal Neoplasms, Carcinoma, Renal Cell, Stomach Neoplasms, Small Cell Lung Carcinoma, Hodgkin Disease, Pancreatic Neoplasms, Triple Negative Breast Neoplasms, Urinary Bladder Neoplasms, Prostatic Neoplasms, Lymphoma, Extranodal NK-T-Cell, Colorectal Neoplasms, Lymphoma, Lymphoma, T-Cell, Carcinoma, Non-Small-Cell Lung, Adenocarcinoma, Carcinoma, Hepatocellular, Melanoma

TQB-2450

APL-502, CBT-502, TQ-B2450

Phase 3 Clinical

Cbt

Liver Neoplasms, Solid tumours, Lymphoma, B-Cell, Biliary Tract Neoplasms, Head and Neck Neoplasms, Carcinoma, Renal Cell, Squamous Cell Carcinoma of Head and Neck, Genital Diseases, Female, Triple Negative Breast Neoplasms, Small Cell Lung Carcinoma, Hodgkin Disease, Carcinoma, Ovarian Epithelial, Stroke, Cholangiocarcinoma, Nasopharyngeal Carcinoma, Peritoneal Neoplasms, Endometrial Neoplasms, Fallopian Tube Neoplasms, Lymphoma, Lung Neoplasms, Uterine Cervical Neoplasms, Adenocarcinoma, Melanoma, Carcinoma, Non-Small-Cell Lung

BMS-936559

MDX-1105, BMS-936559

Phase 3 Clinical

Bristol-Myers Squibb Company

Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Shock, Septic, Hodgkin Disease, Sepsis, Multiple Myeloma, Lymphoma, Non-Hodgkin, Carcinoma, Non-Small-Cell Lung, Melanoma

References


Title

Authors

Source

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Acta Pharmacol. Sin. 26:462-468(2005)

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J. Proteome Res. 8:651-661(2009)

CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity

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Nature 549:101-105(2017)

Aberrant PD-L1 expression through 3'-UTR disruption in multiple cancers

Kataoka K., Shiraishi Y., Takeda Y., Sakata S., Matsumoto M., Nagano S., Maeda T., Nagata Y., Kitanaka A., Mizuno S., Tanaka H., Chiba K., Ito S., Watatani Y., Kakiuchi N., Suzuki H., Yoshizato T., Yoshida K., Ogawa S.,

Nature 534:402-406(2016)