PD-1

Synonyms

Programmed cell death protein 1, CD279, hPD-1, PDCD1, Programmed Cell Death 1, Systemic Lupus Erythematosus Susceptibility 2, Protein PD-1, PD1, Programmed Cell Death 1 Protein, CD279 Antigen, HPD-L, HSLE1, SLEB2, PD-1, Programmed Cell Death 1 Receptor

Description

Programmed cell death protein 1 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. This prevents autoimmune diseases, but it can also prevent the immune system from killing cancer cells.Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self . Delivers inhibitory signals upon binding to ligands CD274/PDCD1L1 and CD273/PDCD1LG2 . Following T-cell receptor (TCR) engagement, PDCD1 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation. Suppresses T-cell activation through the recruitment of PTPN11/SHP-2: following ligand-binding, PDCD1 is phosphorylated within the ITSM motif, leading to the recruitment of the protein tyrosine phosphatase PTPN11/SHP-2 that mediates dephosphorylation of key TCR proximal signaling molecules, such as ZAP70, PRKCQ/PKCtheta and CD247/CD3zeta.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 CD274/PDCD1L1 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

In Vivo

Drug Information

Launched drugs: 8
Drugs in clinical trials: 73
Latest Research Phase: Approved

Drug Name

Code

Phase

Company

Indications

Clinical Trials

Prolgolimab

BCD-100

Approved

Biocad

Carcinoma, Non-Small-Cell Lung, Melanoma, Uterine Cervical Neoplasms

Tislelizumab

BGB-A317

Approved

Beigene Ltd

Lymphoma, T-Cell, Peripheral, Solid tumours, Head and Neck Neoplasms, Lymphoma, B-Cell, Marginal Zone, Carcinoma, Renal Cell, Esophageal Neoplasms, Stomach Neoplasms, Carcinoma, Transitional Cell, Hodgkin Disease, Lymphoma, Large B-Cell, Diffuse, Urinary Bladder Neoplasms, Breast Neoplasms, Lymphoma, Extranodal NK-T-Cell, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Lymphoma, Lymphoma, T-Cell, Cutaneous, Esophageal Squamous Cell Carcinoma, Carcinoma, Squamous Cell, Lymphoma, T-Cell, Lymphoma, Large-Cell, Anaplastic, Lung Neoplasms, Carcinoma, Hepatocellular, Leukemia, Lymphocytic, Chronic, B-Cell, Melanoma, Carcinoma, Non-Small-Cell Lung, Uterine Cervical Neoplasms

Camrelizumab

SHR-1210, INCSHR-1210, HR-301210

Approved

Suzhou Suncadia Biopharmaceuticals Co Ltd, Jiangsu Hengrui Medicine Co Ltd

Solid tumours, Ovarian Neoplasms, Carcinoma, Bronchogenic, Esophageal Neoplasms, Bronchial Neoplasms, Carcinoma, Renal Cell, Stomach Neoplasms, Hodgkin Disease, Carcinoma, Transitional Cell, Triple Negative Breast Neoplasms, Lung Diseases, Nasopharyngeal Carcinoma, Breast Neoplasms, Lymphoma, Extranodal NK-T-Cell, Respiratory Tract Neoplasms, Genital Neoplasms, Female, Urologic Neoplasms, Lung Neoplasms, Endometrial Neoplasms, Esophageal Squamous Cell Carcinoma, Carcinoma, Squamous Cell, Carcinoma, Non-Small-Cell Lung, Melanoma, Gastrointestinal Neoplasms, Uterine Cervical Neoplasms, Carcinoma, Hepatocellular

Dostarlimab

WBP-285, TSR-042, ANB-011

Approved

Anaptysbio

Ovarian Neoplasms, Neoplasms, Peritoneal Neoplasms, Endometrial Neoplasms, Fallopian Tube Neoplasms, Carcinoma, Non-Small-Cell Lung, Uterine Cervical Neoplasms

Sintilimab

IBI-308

Approved

Innovent Biologics(Suzhou) Co Ltd

Solid tumours, Esophageal Neoplasms, Neoplasms, Adenocarcinoma of Lung, Hodgkin Disease, Osteosarcoma, Lymphoma, Extranodal NK-T-Cell, Colorectal Neoplasms, Lung Neoplasms, Esophageal Squamous Cell Carcinoma, Carcinoma, Non-Small-Cell Lung, Melanoma, Uterine Cervical Neoplasms, Carcinoma, Hepatocellular

Anti-PD1/anti-TIM3 bispecific antibody (L&L vision biopharmaceuticals)

Nivolumab

BMS-936558-01, MDX-1106, ONO-4538, ono-0123, BMS-936558

Approved

Ono Pharmaceutical Co Ltd, Bristol-Myers Squibb Company

Solid tumours, Head and Neck Neoplasms, Kidney Neoplasms, Hematologic Neoplasms, Liver Neoplasms, Rhabdomyosarcoma, Ependymoma, Ovarian Neoplasms, Chondrosarcoma, Skin Melanoma, Medulloblastoma, Bone Marrow Neoplasms, Leukemia, Lymphoma, B-Cell, Carcinoma, Renal Cell, Stomach Neoplasms, Esophageal Neoplasms, Squamous Cell Carcinoma of Head and Neck, Hepatitis B, Chronic, Carcinoma, Merkel Cell, Irritable Bowel Syndrome, Carcinoma, Hodgkin Disease, Pancreatic Neoplasms, Sepsis, Small Cell Lung Carcinoma, Neoplasms, Glandular and Epithelial, Carcinoma, Transitional Cell, Skin Neoplasms, Clostridium Infections, Triple Negative Breast Neoplasms, Colonic Neoplasms, Glioblastoma, Adenocarcinoma of Lung, Urinary Bladder Neoplasms, Mesothelioma, Multiple Myeloma, Prostatic Neoplasms, Castration-Resistant, Adrenocortical Carcinoma, Breast Neoplasms, Brain Neoplasms, Sarcoma, Ewing, Microsatellite Instability, Prostatic Neoplasms, Neuroblastoma, Cholangiocarcinoma, Hepatitis B, Sarcoma, Lymphoma, Mantle-Cell, Diarrhea, Colorectal Neoplasms, Ureteral Neoplasms, Genital Neoplasms, Female, Urologic Neoplasms, Peritoneal Neoplasms, Hepatitis C, Lung Neoplasms, Lymphoma, Lymphoma, Non-Hodgkin, Esophageal Squamous Cell Carcinoma, Glioma, Endometrial Neoplasms, Urogenital Neoplasms, Carcinoma, Squamous Cell, Fallopian Tube Neoplasms, Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis, Melanoma, Carcinoma, Hepatocellular, Uterine Cervical Neoplasms, Adenocarcinoma, Large intestine neoplasm, Thyroid Cancer, Papillary

Toripalimab

JS-001, SO-001, TAB-001

Approved

Shanghai Junshi Biosciences Co Ltd, Suzhou Union Biopharm Biosciences Co Ltd

Solid tumours, Kidney Neoplasms, Stomach Neoplasms, Squamous Cell Carcinoma of Head and Neck, Esophageal Neoplasms, Carcinoma, Transitional Cell, Triple Negative Breast Neoplasms, Small Cell Lung Carcinoma, Liposarcoma, Urinary Bladder Neoplasms, Neuroendocrine Tumors, Nasopharyngeal Carcinoma, Lymphoma, Esophageal Squamous Cell Carcinoma, Carcinoma, Hepatocellular, Carcinoma, Non-Small-Cell Lung, Melanoma

Cemiplimab

REGN-2810, SAR-439684

Approved

Regeneron Pharmaceuticals Inc

Ovarian Neoplasms, Solid tumours, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Basal Cell, Carcinoma, Renal Cell, Glioblastoma, Hodgkin Disease, Skin Neoplasms, Central Nervous System Neoplasms, Prostatic Neoplasms, Hepatitis B, Diffuse Intrinsic Pontine Glioma, Peritoneal Neoplasms, Carcinoma, Squamous Cell, Lymphoma, Glioma, Fallopian Tube Neoplasms, Endometrial Neoplasms, Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis, Melanoma, Carcinoma, Hepatocellular, Uterine Cervical Neoplasms

SSI-361

LVGN-3616, SSI-361

Lyvgen Biopharma(HK)Ltd

References

Title

Authors

Source

A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans

Prokunina L., Castillejo-Lopez C., Oberg F., Gunnarsson I., Berg L., Magnusson V., Brookes A.J., Tentler D., Kristjansdottir H., Grondal G., Bolstad A.I., Svenungsson E., Lundberg I., Sturfelt G., Jonssen A., Truedsson L., Lima G., Alcocer-Varela J., Alarcon-Riquelme M.E.,

Nat. Genet. 32:666-669(2002)

Complete sequencing and characterization of 21,243 full-length human cDNAs

Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., Sugano S.,

Nat. Genet. 36:40-45(2004)

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)

The MGC Project Team,

Genome Res. 14:2121-2127(2004)

The role of the PD-1 pathway in autoimmunity and peripheral tolerance

Fife B.T., Pauken K.E.,

Ann. N. Y. Acad. Sci. 1217:45-59(2011)

Safety, activity, and immune correlates of anti-PD-1 antibody in cancer

Topalian S.L., Hodi F.S., Brahmer J.R., Gettinger S.N., Smith D.C., McDermott D.F., Powderly J.D., Carvajal R.D., Sosman J.A., Atkins M.B., Leming P.D., Spigel D.R., Antonia S.J., Horn L., Drake C.G., Pardoll D.M., Chen L., Sharfman W.H., Sznol M.,

N. Engl. J. Med. 366:2443-2454(2012)

Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial

Robert C., Ribas A., Wolchok J.D., Hodi F.S., Hamid O., Kefford R., Weber J.S., Joshua A.M., Hwu W.J., Gangadhar T.C., Patnaik A., Dronca R., Zarour H., Joseph R.W., Boasberg P., Chmielowski B., Mateus C., Postow M.A., Daud A.,

Lancet 384:1109-1117(2014)

Structure and Dynamics of PD-L1 and an Ultra-High-Affinity PD-1 Receptor Mutant

Pascolutti R., Sun X., Kao J., Maute R.L., Ring A.M., Bowman G.R., Kruse A.C.,

Structure 24:1719-1728(2016)

Structural basis for blocking PD-1-mediated immune suppression by therapeutic antibody pembrolizumab

Na Z., Yeo S.P., Bharath S.R., Bowler M.W., Balikci E., Wang C.I., Song H.,

Cell Res. 27:147-150(2017)

An unexpected N-terminal loop in PD-1 dominates binding by nivolumab

Tan S., Zhang H., Chai Y., Song H., Tong Z., Wang Q., Qi J., Wong G., Zhu X., Liu W.J., Gao S., Wang Z., Shi Y., Yang F., Gao G.F., Yan J.,

Nat. Commun. 8:14369-14369(2017)

Structure and chromosomal localization of the human PD-1 gene (PDCD1)

Shinohara T., Taniwaki M., Ishida Y., Kawaich M., Honjo T.,

Genomics 23:704-706(1994)

What's Next for the RenMice™ HiTS Platform?

Please stay tuned for the latest progress of our RenMice™ HiTS Platform. We are open to co-development programs to discover novel antibody therapeutics.
Please contact our team if you are interested in learning more about the HiTS Platform or would like to explore partnership.