Generation and Characterization of Four Novel Monoclonal Antibodies Against Human Programmed Death-1 Molecule

Hybridoma ◽  
2010 ◽  
Vol 29 (2) ◽  
pp. 153-160 ◽  
Author(s):  
Yongjing Chen ◽  
Zhenhua Hu ◽  
Qin Wang ◽  
Yan Ge ◽  
Lixiong Bai ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Programmed Death ◽  
Programmed Death 1

scholarly journals A212 EXPRESSION AND CHARACTERIZATION OF SOLUBLE PEKIN DUCK PROGRAMMED DEATH-1

2018 ◽  
Vol 1 (suppl_1) ◽  
pp. 371-371
Author(s):  
Q Yao ◽  
K P Fischer ◽  
L Tyrrell ◽  
K S Gutfreund
Keyword(s):  
Pekin Duck ◽  
Programmed Death ◽  
Programmed Death 1

scholarly journals A bridging assay for detection and characterization of anti-drug antibodies to dostarlimab, a new anti-PD-1 therapeutic monoclonal antibody

AAPS Open ◽  
2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Marilyn Patterson ◽  
Lee Anne Beausang ◽  
Bonita Rup ◽  
Ronald R. Bowsher ◽  
Kim Krug ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Statistical Data ◽  
Clinical Sample ◽  
The European Union ◽  
Statistical Data Analysis ◽  
Assay Performance ◽  
Programmed Death ◽  
The Usa ◽  
Programmed Death 1

AbstractDostarlimab (JEMPERLI) is a humanized anti-programmed death 1 (PD-1) immunoglobulin (Ig)G4-kappa monoclonal antibody that binds to the PD-1 receptor and competitively inhibits binding of its ligands, PD-L1 and PD-L2. Dostarlimab was recently approved in the USA and the European Union. Because dostarlimab is a macromolecular therapeutic, it has the potential to elicit the formation of anti-drug antibodies, which have the capability to impact the drug’s safety and efficacy and to alter pharmacokinetics. The immunogenic potential of dostarlimab remains unknown, and it was therefore necessary to develop analytical assays to detect and characterize anti-drug antibodies as a key component in the mitigation of immunogenicity risk. Here, we present the development and optimization of a 3-tiered electrochemiluminescense bridging assay for the investigation of dostarlimab clinical immunogenicity. In this work, the full details of the method, statistical data analysis and cut point determinations, assay performance during clinical sample analysis, and associated regulatory expectations are discussed. The full validation of this 3-tier anti-drug antibody assay enabled dostarlimab immunogenicity evaluation in clinical studies. Trial registration: Clinicaltrials.gov, NCT02715284. Registered 9 March 2016

Advances of biphenyl small-molecule inhibitors targeting PD-1/PD-L1 interaction in cancer immunotherapy

2021 ◽  
Author(s):  
Roufen Chen ◽  
Dandan Yuan ◽  
JunJie Ma
Keyword(s):  
Monoclonal Antibodies ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Biological Activities ◽  
Treatment Strategies ◽  
Structural Features ◽  
Great Promise ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
High Production Cost

Immunotherapy inhibiting the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) interaction has emerged as one of the most attractive cancer treatment strategies. So far, the clinically used PD-1/PD-L1 inhibitors are monoclonal antibodies, but monoclonal antibodies have several limitations, such as poor pharmacokinetic properties, unchecked immune responses and high production cost. The development of small-molecule inhibitors targeting PD-1/PD-L1 interaction is showing great promise as a potential alternative or complementary therapeutic approach of monoclonal antibodies. In this article, the authors classify the reported biphenyl small-molecule inhibitors into symmetrical and asymmetrical types based on their structural features and further review their representative inhibitors and biological activities, as well as the binding models for providing insight into further exploration of more potent biphenyl small-molecule inhibitors targeting PD-1/PD-L1 interaction.

Molecular cloning, expression and characterization of Pekin duck programmed death-1

Gene ◽  
2019 ◽  
Vol 702 ◽  
pp. 182-193
Author(s):  
Qingxia Yao ◽  
Karl P. Fischer ◽  
D. Lorne Tyrrell ◽  
Klaus S. Gutfreund
Keyword(s):  
Molecular Cloning ◽  
Pekin Duck ◽  
Programmed Death ◽  
Programmed Death 1

scholarly journals Characterization of Programmed Death-1 Homologue-1 (PD-1H) Expression and Function in Normal and HIV Infected Individuals

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e109103 ◽  
Author(s):  
Preeti Bharaj ◽  
Harendra Singh Chahar ◽  
Ogechika K. Alozie ◽  
Lizette Rodarte ◽  
Anju Bansal ◽  
...  
Keyword(s):  
Programmed Death ◽  
Programmed Death 1 ◽  
And Function

scholarly journals Nephrotoxicity in patients with solid tumors treated with anti-PD-1/PD-L1 monoclonal antibodies: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Han Li ◽  
Jinsheng Xu ◽  
Yaling Bai ◽  
Shenglei Zhang ◽  
Meijuan Cheng ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Solid Tumors ◽  
Meta Analysis ◽  
Kidney Injury ◽  
Cochrane Library ◽  
Randomized Controlled ◽  
Programmed Death ◽  
Registration Number ◽  
Programmed Death 1 ◽  
The Cochrane Library

SummaryBackground Programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) have dramatically improved cancer therapy for many patients. Adverse kidney effects have been found to be an important complication but have unclear mechanisms. Methods We searched Embase, PubMed, and the Cochrane Library to identify potential eligible studies. All included studies were randomized controlled trials (RCTs) examining patients with solid tumors treated with anti-PD-1/PD-L1 monoclonal antibodies (mAbs) and/or chemotherapy. The relative risk (RR) was used to assess the risk of nephrotoxic events. Results We included 27 clinical trials (15,063 patients). Compared with chemotherapy, the RR of all-grade nephritis was significantly increased with anti-PD-1/PD-L1 mAbs (RR = 2.77, 95% CI: 1.09–6.99, P = 0.03). Furthermore, anti-PD-1/PD-L1 mAbs plus chemotherapy can significantly increase the RR of all-grade nephritis (RR = 2.99, 95% CI: 1.07–8.35, P = 0.04). There was also a significant increase in the RRs of all-grade increased blood creatinine (RR = 1.88, 95% CI: 1.24–2.86, P = 0.003) and acute kidney injury (AKI) (RR =3.35, 95% CI: 1.48–7.60, P = 0.004). Conclusions Anti-PD-1/PD-L1 mAbs can significantly increase nephrotoxicity in patients with solid tumors, especially when combined with chemotherapy. During the application of these drugs, we should remain aware of nephrotoxicity for better efficacy. Trial registration number and date of registration Not applicable.

Refolding and Characterization of Recombinant Human GST-PD-1 Fusion Protein Expressed in Escherichia coli

2004 ◽  
Vol 36 (2) ◽  
pp. 141-146 ◽  
Author(s):  
Da-Wei Li ◽  
Jian-Feng Yu ◽  
Yong-Jing Chen ◽  
Hong-Bing Ma ◽  
Zheng-Fei Wang ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Costimulatory Molecule ◽  
Size Exclusion ◽  
Activated T Cells ◽  
E Coli ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Set Up

Abstract Programmed death-1 (PD-1) is a costimulatory molecule of CD28 family expressed on activated T, B and myeloid cells. The engagement of PD-1 with its two ligands, PD-L1 and PD-L2, inhibits proliferation of T cell and production of a series of its cytokines. The blockade of PD-1 pathway is involved in antiviral and antitumoral immunity. In this study, human PD-1 cDNA encoding extracellular domain was amplified and cloned into expression plasmid pGEX-5x-3. The fusion protein GST-PD-1 was effectively expressed in E. coli BL21 (DE3) as inclusion bodies and a denaturation and refolding procedure was performed to obtain bioactive soluble GST-PD-1. Fusion protein of above 95% purity was acquired by a convenient two-step purification using GST affinity and size exclusion columns. Furthermore, a PD-L1-dependent in vitro bioassay method was set up to characterize GST-PD-1 bioactivity. The results suggested that GST-PD-1 could competently block the interaction between PD-L1 and PD-1 and increase the production of IL-2 and IFN-γ of phytohemagglutinin-activated T cells.

Drug of the year: Programmed Death-1 receptor/Programmed Death-1 Ligand-1 receptor monoclonal antibodies

2013 ◽  
Vol 49 (14) ◽  
pp. 2968-2971 ◽  
Author(s):  
Caroline Robert ◽  
Jean-Charles Soria ◽  
Alexander M.M. Eggermont
Keyword(s):  
Monoclonal Antibodies ◽  
Programmed Death ◽  
Programmed Death 1

Characterization of Monoclonal Anti-human Factor VII Antibody (B101/B1) that Recognized Three-dimensional Structures near Arg at Position 79 in the First EGF-like Domain

1998 ◽  
Vol 79 (01) ◽  
pp. 104-109 ◽  
Author(s):  
Osamu Takamiya
Keyword(s):  
Monoclonal Antibodies ◽  
Tissue Factor ◽  
Human Factor ◽  
Solid Phase ◽  
Three Dimensional ◽  
Coagulation Factors ◽  
Factor Vii ◽  
Dimensional Structure ◽  
Epidermal Growth

SummaryMurine monoclonal antibodies (designated hVII-B101/B1, hVIIDC2/D4 and hVII-DC6/3D8) directed against human factor VII (FVII) were prepared and characterized, with more extensive characterization of hVII-B101/B1 that did not bind reduced FVIIa. The immunoglobulin of the three monoclonal antibodies consisted of IgG1. These antibodies did not inhibit procoagulant activities of other vitamin K-dependent coagulation factors except FVII and did not cross-react with proteins in the immunoblotting test. hVII-DC2/D4 recognized the light chain after reduction of FVIIa with 2-mercaptoethanol, and hVIIDC6/3D8 the heavy chain. hVII-B101/B1 bound FVII without Ca2+, and possessed stronger affinity for FVII in the presence of Ca2+. The Kd for hVII-B101/B1 to FVII was 1.75 x 10–10 M in the presence of 5 mM CaCl2. The antibody inhibited the binding of FVII to tissue factor in the presence of Ca2+. hVII-B101/B1 also inhibited the activation of FX by the complex of FVIIa and tissue factor in the presence of Ca2+. Furthermore, immunoblotting revealed that hVII-B101/B1 reacted with non-reduced γ-carboxyglutaminic acid (Gla)-domainless-FVII and/or FVIIa. hVII-B101/B1 showed a similar pattern to that of non-reduced proteolytic fragments of FVII by trypsin with hVII-DC2/D4 on immunoblotting test. hVII-B101/B1 reacted differently with the FVII from the dysfunctional FVII variant, FVII Shinjo, which has a substitution of Gln for Arg at residue 79 in the first epidermal growth factor (1st EGF)-like domain (Takamiya O, et al. Haemosta 25, 89-97,1995) compared with normal FVII, when used as a solid phase-antibody for ELISA by the sandwich method. hVII-B101/B1 did not react with a series of short peptide sequences near position 79 in the first EGF-like domain on the solid-phase support for epitope scanning. These results suggested that the specific epitope of the antibody, hVII-B101/B1, was located in the three-dimensional structure near position 79 in the first EGF-like domain of human FVII.

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