Residue Specific Binding Analysis of PD-L1 to Its Monoclonal Antibodies by Computational Alanine Scanning

2021 ◽  
Author(s):  
Wei Wen ◽  
Dading Huang ◽  
Jinxiao Bao ◽  
John Z.H. Zhang
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Monoclonal Antibodies ◽  
Programmed Cell Death ◽  
Cancer Patients ◽  
Specific Binding ◽  
Checkpoint Proteins ◽  
Programmed Cell Death 1 ◽  
Computational Alanine Scanning ◽  
Immune Checkpoint Proteins

Programmed cell death 1 receptor (PD-1) on the surface of T cells and its ligand 1 (PD-L1) are immune checkpoint proteins. Treating cancer patients with inhibitors blocking this checkpoint has...

scholarly journals Soluble Programmed Cell Death-1 Predicts Hepatocellular Carcinoma Development During Nucleoside Analogue Treatment

2021 ◽  
Author(s):  
Ritsuzo Kozuka ◽  
Masaru Enomoto ◽  
Minh Phuong Dong ◽  
Hoang Hai ◽  
Le Thi Thanh Thuy ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Rank Test ◽  
Baseline Serum ◽  
Checkpoint Proteins ◽  
Programmed Cell Death 1 ◽  
Chronic Hepatitis B Virus ◽  
Immune Checkpoint Proteins

Abstract Soluble immune checkpoint molecules are emerging novel mediators of immune regulation. However, it is unclear whether soluble immune checkpoint proteins affect the development of hepatocellular carcinoma (HCC) during nucleos(t)ide analogue (NA) treatment in patients with chronic hepatitis B virus infection. This study included 122 NA-naïve patients who received NA therapy. We assessed the associations of clinical factors, including soluble immune checkpoint proteins, with HCC development during NA treatment. The baseline serum concentrations of 16 soluble immune checkpoint proteins were measured using multiplexed fluorescent bead-based immunoassay. In total, 13 patients developed HCC during the follow-up period (median duration, 4.3 years). Of the 16 proteins, soluble inducible T-cell co-stimulator (≥ 164.71 pg/mL; p = 0.014), soluble programmed cell death-1 (sPD-1) (≤ 447.27 pg/mL; p = 0.031), soluble CD40 (≤ 493.68 pg/mL; p = 0.032), and soluble herpes virus entry mediator (≤ 2,470.83 pg/mL; p = 0.038) were significantly associated with HCC development (log-rank test). In a multivariate analysis, an sPD-1 level ≤ 447.27 pg/mL (p = 0.014; hazard ratio [HR], 4.537) and α-fetoprotein level ≥ 6.4 ng/mL (p = 0.040; HR, 5.524) were independently and significantly associated with HCC development. sPD-1 is a novel predictive biomarker for HCC development during NA treatment.

scholarly journals Soluble programmed cell death-1 predicts hepatocellular carcinoma development during nucleoside analogue treatment

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Ritsuzo Kozuka ◽  
Masaru Enomoto ◽  
Minh Phuong Dong ◽  
Hoang Hai ◽  
Le Thi Thanh Thuy ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Rank Test ◽  
Baseline Serum ◽  
Checkpoint Proteins ◽  
Programmed Cell Death 1 ◽  
Chronic Hepatitis B Virus ◽  
Immune Checkpoint Proteins

AbstractSoluble immune checkpoint molecules are emerging novel mediators of immune regulation. However, it is unclear whether soluble immune checkpoint proteins affect the development of hepatocellular carcinoma (HCC) during nucleos(t)ide analogue (NA) treatment in patients with chronic hepatitis B virus infection. This study included 122 NA-naïve patients who received NA therapy. We assessed the associations of clinical factors, including soluble immune checkpoint proteins, with HCC development during NA treatment. The baseline serum concentrations of 16 soluble immune checkpoint proteins were measured using multiplexed fluorescent bead-based immunoassay. In total, 13 patients developed HCC during the follow-up period (median duration, 4.3 years). Of the 16 proteins, soluble inducible T-cell co-stimulator (≥ 164.71 pg/mL; p = 0.014), soluble programmed cell death-1 (sPD-1) (≤ 447.27 pg/mL; p = 0.031), soluble CD40 (≤ 493.68 pg/mL; p = 0.032), and soluble herpes virus entry mediator (≤ 2470.83 pg/mL; p = 0.038) were significantly associated with HCC development (log-rank test). In multivariate analysis, an sPD-1 level ≤ 447.27 pg/mL (p = 0.014; hazard ratio [HR], 4.537) and α-fetoprotein level ≥ 6.4 ng/mL (p = 0.040; HR, 5.524) were independently and significantly associated with HCC development. Pre-treatment sPD-1 is a novel predictive biomarker for HCC development during NA treatment.

scholarly journals Response to Programmed Cell Death-1 Blockade in a Murine Melanoma Syngeneic Model Requires Costimulation, CD4, and CD8 T Cells

2016 ◽  
Vol 4 (10) ◽  
pp. 845-857 ◽  
Author(s):  
Blanca Homet Moreno ◽  
Jesse M. Zaretsky ◽  
Angel Garcia-Diaz ◽  
Jennifer Tsoi ◽  
Giulia Parisi ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cd8 T Cells ◽  
Murine Melanoma ◽  
Programmed Cell Death 1 ◽  
Syngeneic Model

Side effects of immune-checkpoint inhibitors: Can multiple side effects be seen in a patient?

2021 ◽  
pp. 107815522110381
Author(s):  
Esra Özyurt ◽  
Serhat Özçelik ◽  
Heves Sürmeli ◽  
Mehmet Çelik ◽  
Murat Ayhan ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Side Effects ◽  
Programmed Cell Death ◽  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Host Cells ◽  
Immunoglobulin G4 ◽  
Programmed Cell Death 1 ◽  
Recurrent Renal Cell Carcinoma

Introduction Nivolumab is a human immunoglobulin G4 monoclonal antibody that inhibits programmed cell death-1 activity by binding to the programmed cell death-1 receptors. Cancer cells express increased number of programmed cell death-1 ligands and this allows them to escape the cytotoxic effects of the T cells. Therefore, the negative programmed cell death-1 receptor signal regulates T-cell proliferation and activation is disrupted. However, this change in the activity of the T cells can cause them to lose their ability to recognize host cells. The immune response enabled by these agents has led to side effects, commonly known as “immune-related adverse events.” Case report We report a case of a 66-year-old male patient who was treated with nivolumab for recurrent renal cell carcinoma presented with hepatitis and adrenalitis. Three weeks after starting nivolumab, the patient had abdominal pain and weakness, and then aspartate and alanine transaminase levels were found to be elevated. Management and outcome Hepatitis was predicted to be due to nivolumab, because other causes were excluded. He started using oral methylprednisolone and then, hepatitis improved. However, while receiving methylprednisolone treatment, fludrocortisone was started with the pre-diagnosis of adrenalitis due to the persistence of fatigue, weakness, and hyponatremia and hyperkalemia. With both treatments, the patient's symptoms and sodium and potassium level returned to normal. Discussion This case emphasizes the need for patient's education and awareness of immune-related adverse events, and the importance of understanding the management of life-threatening complications of the checkpoint inhibitors, because these side effects require prompt recognition and treatment.

scholarly journals Anti-programmed cell death-1 (PD-1) monoclonal antibodies involve reversible cranial dura matter

2021 ◽  
Vol 2021 (9) ◽  
Author(s):  
Hiroshi Kataoka ◽  
Daisuke Shimada ◽  
Hitoki Nanaura ◽  
Kazuma Sugie
Keyword(s):  
Central Nervous System ◽  
Cell Death ◽  
Nervous System ◽  
Monoclonal Antibodies ◽  
Programmed Cell Death ◽  
Adverse Effects ◽  
Neuromuscular Disorders ◽  
Neurological Complications ◽  
Programmed Cell Death 1 ◽  
The Central Nervous System

ABSTRACT This case is the first document to describe a patient receiving anti-programmed cell death 1 (PD-1) antibodies which showed cranial dura matter involvement. According to the increasing use of anti-PD-1 monoclonal antibodies, adverse effects can occur in several organs since its ligand PD-L1 and PD-L2 are expressed in a wide variety of tissues. The estimated rate of neurological complications is 1–4.2% of patients, and neuromuscular disorders are the most common. Adverse effects on the central nervous system including encephalitis are less frequent. Here, a patient receiving anti-PD-1 antibodies showed cranial dura matter involvement, and the dura enhancement on MRI was resolved by withdrawal of the treatment with anti-PD-1 antibodies only.

scholarly journals Mice lacking Programmed cell death-1 show a role for CD8+ T cells in long-term immunity against blood-stage malaria

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Joshua M. Horne-Debets ◽  
Deshapriya S. Karunarathne ◽  
Rebecca J. Faleiro ◽  
Chek Meng Poh ◽  
Laurent Renia ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cd8 T Cells ◽  
Blood Stage ◽  
Programmed Cell Death 1 ◽  
Blood Stage Malaria
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