Journal: Journal of Medicinal Chemistry

Article Title: Terphenyl-Based Small-Molecule Inhibitors of Programmed Cell Death-1/Programmed Death-Ligand 1 Protein–Protein Interaction

doi: 10.1021/acs.jmedchem.1c00957

Figure Lengend Snippet: Effect of 8j and 8h on the reactivation of primary T-cells preblocked by PD-L1-overexpressing cells. (A) Expression of early (CD69), intermediate (CD25, HLA-DR), and late (PD-1) T-cell activation/exhaustion markers was determined by flow cytometry. PBMCs from healthy donors were exposed to CHO/TCRAct/PD-L1 cells for 2 days in the presence of durvalumab (durva), atezolizumab (atezo), avelumab (avelu), or increasing concentrations of 8j and 8h (concentrations: 0.1, 0.5, or 2.5 μM). ø indicates untreated cells. The graphs show fractions of positive cells and represents cumulative data from four donors. Statistical significance was analyzed with one-way ANOVA, followed by Fisher’s posthoc test: * p < 0.05, ** p < 0.01, *** p < 0.01. (B) Accumulation of the indicated cytokines in culture media from the TCA assay. The graphs show mean ± standard error of the mean values from four independent donors. For each donor, the data were normalized to untreated coculture of PBMCs and CHO/TCRAct cells as a determinant of donor-dependent cytokine level independent of the PD-L1/PD-1 axis. Statistical significance was analyzed with one-way ANOVA, followed by the Fisher posthoc test: * p < 0.05, ** p < 0.01, *** p < 0.001.

Article Snippet: PBMCs were added at an amount of 3 × 10 5 to CHO, CHO/TCRAct, or CHO/TCRAct/PD-L1 cells preseeded on 24-well plates in the presence of either anti-PD-L1 mAbs (at the final concentration 5 μg/mL): durvalumab (Selleckchem), atezolizumab (Selleckchem), or avelumab (MedChemExpress) or tested compounds at the concentrations 0.1, 0.5, and 2.5 μM.

Techniques: Expressing, Activation Assay, Flow Cytometry

Journal: OncoTargets and therapy

Article Title: PD-1 as an emerging therapeutic target in renal cell carcinoma: current evidence

doi: 10.2147/OTT.S48443

Figure Lengend Snippet: PD-1- or PD-L1-blocking agents in clinical trails

Article Snippet: MSB0010718C , Merck KGaA , Fully human IgG1 mAb , Phase I.

Techniques: Modification

Journal: Cell Research

Article Title: Structural basis of anti-PD-L1 monoclonal antibody avelumab for tumor therapy

doi: 10.1038/cr.2016.102

Figure Lengend Snippet: Detailed binding of avelumab to hPD-L1 for the blockade of hPD-1/hPD-L1 interaction. (A) Overall structure of the hPD-L1/avelumab-scFv complex. hPD-L1 (only the mAb-binding IgV domain is depicted) is shown as surface diagram in light blue, and the heavy (VH) and light (VL) chains of scFv are shown as cartoon representations in pink and cyan, respectively. The CDR1, CDR2 and CDR3 loops of VH are colored in yellow, green and hot pink, respectively. The CDR1 and CDR3 loops of VL are colored in purple and blue, respectively. (B) The epitope residues in hPD-L1 are denoted in black characters. Residues contacted by the avelumab-scFv VH or VL are colored in pink and cyan, respectively, whereas residues contacted by both chains are colored in lemon. (C) The residues of avelumab-scFv contacting hPD-L1 are colored in yellow for VH and colored in magenta for VL. (D) The detailed interactions in hPD-L1/avelumab-scFv complex. Residues involved in the hydrogen bond interaction are shown as sticks and labeled. Hydrogen bonds are shown as dash lines. (E) Superposition of the hPD-L1/avelumab-scFv complex structure with hPD-1/hPD-L1 complex structure. hPD-1 is shown in orange and avelumab-scFv VH in pink, VL in cyan, respectively. (F) Binding surface of hPD-L1 by hPD-1 or avelumab. The binding residues on hPD-L1 are colored in orange, whereas residues contacted by the avelumab-scFv VH or VL are colored in pink or cyan, respectively, and the overlapping residues bound by both the receptor hPD-1 and avelumab are colored in red.

Article Snippet: As one of the PD-L1 targeting antibodies, avelumab is a human IgG1 antibody with ADCC activity developed by Merck (Darmstadt, Germany) and Pfizer, which is now in multiple phase III clinical trials against non-small cell lung cancer ( {"type":"clinical-trial","attrs":{"text":"NCT02395172","term_id":"NCT02395172"}} NCT02395172 ), advanced renal cell cancer ( {"type":"clinical-trial","attrs":{"text":"NCT02684006","term_id":"NCT02684006"}} NCT02684006 ) and gastric cancer ( {"type":"clinical-trial","attrs":{"text":"NCT02625610","term_id":"NCT02625610"}} NCT02625610 ) 6 .

Techniques: Binding Assay, Labeling

Journal: Frontiers in Immunology

Article Title: NK Cell-Based Immune Checkpoint Inhibition

doi: 10.3389/fimmu.2020.00167

Figure Lengend Snippet: Clinical trials evaluating the safety, tolerability and efficacy of NK cell-based immune checkpoint inhibitors or potential immune checkpoint inhibitors for NK cell-based immunotherapy.

Article Snippet: , NCT03252938 , I, Non-randomized , IKF Klinische Krebsforschung GmbH at Krankenhaus Nordwest , 50 , IMP321 (LAG-3Ig fusion protein), avelumab , IMP321 alone or IMP321 plus avelumab , Recruiting , Solid tumor peritoneal carcinomatosis , August 17, 2017.

Techniques: Wilms Tumor Assay

Journal: Cancers

Article Title: Harnessing NK Cell Checkpoint-Modulating Immunotherapies

doi: 10.3390/cancers12071807

Figure Lengend Snippet: Clinical trials combining checkpoint receptor based targeting with or without biologicals

Article Snippet: , Avelumab , Solid Tumors, Peritoneal Carcinomatosis , Phase 1, Nonrandomized , Feasibility and Safety of IMP321 for Advanced Stage Solid Tumors , 26 , Active, not recruiting , InstitutfürKlinischeKrebsforschung IKF GmbH at KrankenhausNordwest , NCT03252938.

Techniques: Clinical Proteomics, Drug discovery, Transplantation Assay, Biomarker Discovery, Activity Assay, Adjuvant, Comparison, Sequencing, Protein Binding