Recombinant Human PD-1 Protein (C-Fc)

Name: Recombinant Human PD-1 Protein (C-Fc)
Brand: Beta LifeScience
SKU: BL-0235NP
Availability: InStock

BL-0235NP: Greater than 95% as determined by reducing SDS-PAGE. (QC verified)

Collections: Antibody / cell therapy targets, Antibody therapeutic / adc target proteins, Co-inhibitory receptors, Featured immune checkpoint protein molecules, Immune checkpoint proteins, Recombinant proteins

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Product Overview

Description	Recombinant Human Programmed Cell Death Protein 1 is produced by our Mammalian expression system and the target gene encoding Pro21-Gln167 is expressed with a human IgG1 Fc tag at the C-terminus.
Accession	Q15116
Synonym	Programmed cell death protein 1; PDCD1; PD-1; hPD-1; CD279
Gene Background	Programmed cell death protein 1(PDCD1) is a single-pass type I membrane protein and contains 1 Ig-like V-type domain. PD-1 is a member of the extended CD28/CTLA-4 family of T cell regulators. PDCD1 inhibits the T-cell proliferation and production of related cytokines including IL-1, IL-4, IL-10 and IFN-γ by suppressing the activation and transduction of PI3K/AKT pathway. In addition, coligation of PDCD1 inhibits BCR-mediating signal by dephosphorylating key signal transducer. PDCD1 has been suggested to be involved in lymphocyte clonal selection and peripheral tolerance, and thus contributes to the prevention of autoimmune diseases. As a cell surface molecule, PDCD1 regulates the adaptive immune response. Engagement of PD-1 by its ligands PD-L1 or PD-L2 transduces a signal that inhibits T-cell proliferation, cytokine production, and cytolytic function.
Molecular Mass	43.6 KDa
Apmol Mass	60-70 KDa, reducing conditions
Formulation	Lyophilized from a 0.2 μm filtered solution of PBS, pH 7.4.
Endotoxin	Less than 0.1 ng/µg (1 EU/µg) as determined by LAL test.
Purity	Greater than 95% as determined by reducing SDS-PAGE. (QC verified)
Biological Activity	Not tested
Reconstitution	Always centrifuge tubes before opening. Do not mix by vortex or pipetting. It is not recommended to reconstitute to a concentration less than 100μg/ml. Dissolve the lyophilized protein in distilled water. Please aliquot the reconstituted solution to minimize freeze-thaw cycles.
Storage	Lyophilized protein should be stored at ≤ -20°C, stable for one year after receipt. Reconstituted protein solution can be stored at 2-8°C for 2-7 days. Aliquots of reconstituted samples are stable at ≤ -20°C for 3 months.
Shipping	The product is shipped at ambient temperature. Upon receipt, store it immediately at the temperature listed below.
Usage	For Research Use Only

Target Details

Target Function	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.
Subcellular Location	Cell membrane; Single-pass type I membrane protein.
Database References	HGNC: 8760 OMIM: 109100 KEGG: hsa:5133 STRING: 9606.ENSP00000335062 UniGene: Hs.158297
Associated Diseases	Systemic lupus erythematosus 2 (SLEB2)

Gene Functions References

HLA-G, NRP1, and PD-1, may be involved in the immune response in psoriatic patients PMID: 29790686
Proportions of naive CD4+ T cells were lower in young patients than in age-matched controls, and actually comparable to those in old patients and controls. This was accompanied with increased percentages of memory CD4+ T cells expressing HLA-DR, Ki-67, and PD-1 in young melanoma patients in comparison to the age-matched controls, but not in old patients. PMID: 29546435
This meta-analysis demonstrates the PD-1 rs36084323 A > G polymorphism is associated with decreased cancer risk in Asian PMID: 30249505
there is no significant association between PD1.3G/A - rs11568821 polymorphism and systemic lupus erythematosus or rheumatoid arthritis susceptibility in Southern Brazilian population. PMID: 27914594
SLC18A1 might complement other biomarkers currently under study in relation to programmed cell death protein 1/programmed cell death protein ligand 1 inhibition PMID: 30194079
Structural and functional analyses unexpectedly reveal an N-terminal loop outside the IgV domain of PD-1. This loop is not involved in recognition of PD-L1 but dominates binding to nivolumab, whereas N-glycosylation is not involved in binding at all. PMID: 28165004
This finding suggested the potential application of PD-1 blockade in AML. The present work demonstrated an excellent synergistic tumour therapeutic effect of PD-1 blockade and CTL therapy compared with either treatment alone. PMID: 29962321
High PD-1 expression is associated with Mycobacterium avium complex-induced lung disease. PMID: 28169347
PD-1/PD-L1 expression is a frequent occurrence in poorly differentiated neuroendocrine carcinomas of the digestive system. PMID: 29037958
Results indicated that high-level PD1 expression may be an important factor associated with the immune checkpoint pathway in liver cancer. PMID: 29620156
These results suggest that the PD-1 genotype of the donor plays an important role for the development of acute GvHD after alloHSCT from HLA-identical sibling donors. PMID: 30019128
We conclude that a subgroup of advanced disease ovarian cancer patients with high grade tumors, expressing PD-L1, may be prime candidates for immunotherapy targeting PD-1 signaling PMID: 29843813
Both rs2227982 and rs2227981 polymorphisms were associated with T1 Diabetes (T1D) risk in East Asians, and rs2227982 also had a significant association with glycemic traits, which suggested PDCD1 gene polymorphisms might participate in facilitating T1D risk. [meta-analysis] PMID: 29774466
PD.1 (-538G/A) gene polymorphism is associated with Colon Cancer Risk. PMID: 29580042
The high-affinity PD-1 mutant could compete with the binding of antibodies specific to PD-L1 or PD-L2 on cancer cells. PMID: 29890018
The G allele of rs36084323 of PDCD1 is associated with increased risk of advanced TNM staging of colorectal cancer. PMID: 29652996
promoter methylation of CTLA4, PD-L1, PD-L2, and PD-1 in diffuse lower-grade gliomas (LGG) harboring isocitrate dehydrogenase (IDH) mutation, is reported. PMID: 29396294
Unlike other multiple autoimmune disease associated genetic variants, there was no association between PDCD1 variants and Juvenile Idiopathic Arthritis PMID: 28056736
Alteration of the PD-1/PD-L1 pathway can modulate Treg/Th17 balance in asthmatic children. PMID: 29874664
The expression of PD1 on T cells was elevated in patients with rheumatoid arthritis and was correlated with the disease activity. PMID: 29257239
High expression of programmed death-1 in sentinel lymph nodes is associated with breast cancer. PMID: 29193094
We describe three cases of patients with mRCC treated with anti-PD-1 antibody therapy in combination with targeted therapy (bevacizumab), anti-cytotoxic T lymphocyte antigen 4 therapy (ipilimumab), or radiotherapy. PMID: 29146617
anti-CTLA4/anti-PD-1/PD-L1 combinations versus anti-PD-1/PD-L1 monotherapy was selected as a factor independent of TMB for predicting better RR (77% vs. 21%; P = 0.004) and PFS (P = 0.024). Higher TMB predicts favorable outcome to PD-1/PD-L1 blockade across diverse tumors. PMID: 28835386
The altered soluble (s)PD1 and sICOS serum levels in the different Hepatitis b (HBV) groups may reflect the dysregulation of T cell activation, and may be associated with the HBV pathological process. PMID: 28983583
We found that PD-L1 expression was upregulated following TGF-beta induction; in contrast, it was downregulated by TGF-beta receptor-kinase inhibitors and the MET process. Furthermore, chemo-treatment increased TGF-beta expression and enhances PD-L1 expression via autocrine TGF-beta induced EMT. Analysis of clinical samples revealed a significant relationship between PD-L1 expression and EMT status PMID: 28849209
this study demonstrated that PD-1 may involve in lymph nodes metastasis and promote the understanding of the mechanism of immunotherapies in the non-small cell lung cancer PMID: 28799818
PD-L1 expression in melanoma tumor cells is lower than NSCLC or renal cell carcinoma cells. The higher response rate in melanoma patients treated with PD-1 inhibitors is likely related to PD-L1 in tumor-associated inflammatory cells. Further studies are warranted to validate the predictive role of inflammatory cell PD-L1 expression in melanoma and determine its biological significance PMID: 28223273
Higher PRE PD-1(+) T cells in responders suggest active suppression of an engaged immune system that is disinhibited by anti-PD-1 therapies. Furthermore, immunoprofiling of EDT biopsies for increased PD-L1 expression and immune cell infiltration showed greater predictive utility than PRE biopsies and may allow better selection of patients most likely to benefit from anti-PD-1 therapies and warrants further evaluation PMID: 28512174
PD-1 was overexpressed on CD8+ T-cells from patients with Obstructive Sleep Apnoea in a severity-dependent manner. PMID: 29051270
The results show that the distinctive pathological features of papillary thyroid carcinomas (PTCs), including tumor-infiltrating lymphocytes (TILs), background chronic lymphocytic thyroiditis (CLT), female gender, psammoma bodies, and stromal calcification, are useful parameters for predicting PD-L1 or PD-1 expression. PMID: 28974264
Our results did not show any association between PDCD1 SNPs and the development of juvenile idiopathic arthritis in an Iranian population PMID: 29307156
High expressions of programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) were associated with poor prognosis after surgery. PMID: 29848685
Programmed death-1 polymorphism is associated with risk of esophagogastric junction adenocarcinoma. PMID: 28487496
PD-1 was expressed in 26% of Ewing's sarcoma family of tumor cells and may have prognostic and therapeutic implications PMID: 29445891
We now show that patients with low PD-L1 expression on myeloid cells have improved survival when treated with an antitumor vaccine, suggesting that PD-L1 expression on myeloid cells may be an important predictive biomarker in future clinical trials. Additionally, the combination of PD-1/PD-L1 inhibition and vaccination may increase the efficacy of this immunotherapeutic approach. PMID: 28193626
Lower expression of PD-1 and PD-L1 was associated with better survival in patients who underwent surgery for the primary tumor and had multiple brain metastases PMID: 28201746
PD-1/PD-L pathway inhibits Mycobacterium tuberculosis-specific CD4(+) T-cell functions and phagocytosis of macrophages in active tuberculosis. PMID: 27924827
This study builds optimism that harmonization between assays may be possible, and that the three assays studied could potentially be used interchangeably to identify patients most likely to respond to anti-PD-1/PD-L1 immunotherapies, provided the appropriate clinically defined algorithm and agent are always linked. PMID: 28073845
Results identified an overall low expression of PD-1 and PD-L1 in high-risk prostate cancer tissue. PMID: 28461179
The biopsy tumor key protein measurements demonstrate substantial between-tumor variation in expression ratios of these proteins and suggest that programmed cell death 1 ligand 2 PD-L2 is present in some tumors at levels sufficient to contribute to programmed cell death-1 PD-1-dependent T-cell regulation and possibly to affect responses to PD-1- and programmed cell death 1 ligand 1 PD-L1-blocking drugs. PMID: 28546465
Early phase clinical trials using PD-1 or PD-L1 inhibitors alone or in combination have shown objective tumor responses and durable long-term disease control, in heavily pre-treated patients, notably in the TN subtype. Blockade of PD-1 or PD-L1 shows impressive antitumor activity in some subsets of breast cancer patients PMID: 28799073
Differential expression of immunological markers relating to the PD-1/PD-L1 pathway in blood can be used as potential diagnostic and prognostic markers in ovarian cancers. These data have implications for the development and trial of anti-PD-1/PD-L1 therapy in ovarian cancer. PMID: 27986748
LAG-3+ iTILs are enriched in estrogen receptor-negative breast cancers and represent an independent favorable prognostic factor. In addition, a high proportion of PD-1/PD-L1+ tumors are co-infiltrated with LAG-3+ TILs. PMID: 29045526
An IDO1 inhibitor, epacadostat also demonstrated promising activity in combination with the PD-1 checkpoint inhibitors in other solid tumors, including melanoma, urothelial carcinoma, renal cell carcinoma, and non-small cell lung cancer PMID: 28760910
PD-L1 was positive in tumor cells in 2/13 cases, weak positive in 7/13, and negative in 4/13 cases, respectively PMID: 28807336
we report the first case of immune microenvironment profiling and response to anti-PD-1 in a patient with Renal medullary carcinoma to our knowledge. This case suggests that anti-PD-1 based therapies may have clinical activity in Renal medullary carcinoma PMID: 28105368
We present two cases of metastatic melanoma treated with nivolumab and pembrolizumab (anti PD-1). Both patients developed acute interstitial nephritis during immune checkpoint therapy PMID: 28105370
the positive rate of PD-L2 did not show any differences between primary tumors and metastatic lymph nodes. In multivariate analysis, PD-L1 expression, PD-L2 expression, a low density of CD8(+) T cells in primary tumors, and PD-1 expression on CD8(+) T cells in primary tumors were associated with poor prognosis. PMID: 28754154
Relative to controls, the expression of PD-1 and PD-L1 on peripheral blood and tumor infiltrating T cells increased with disease progression. Upregulation of expression promotes t-cells apoptosis in gastric adenocarcinoma. PMID: 29599324
These data support the combinatorial approach of in situ suppression of the PD-L inhibitory checkpoints with DC-mediated IL15 transpresentation to promote antigen-specific T-cell responses and, ultimately, contribute to graft-versus-tumor immunity PMID: 28637876

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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

To learn more about how to properly dissolve the lyophilized recombinant protein, please visit Lyophilization FAQs.