scholarly journals Review of the Combination Strategies Used in Anti-PD1/PD-L1 Monoclonal Antibody Treatment

2020 ◽  
Vol 185 ◽  
pp. 03009
Author(s):  
Jiaxing Cheng
Keyword(s):  
Death Receptor ◽  
Strategy Development ◽  
Large Individual ◽  
Antibody Treatment ◽  
Programmed Death Ligand 1 ◽  
Combination Strategies ◽  
Therapy Strategy ◽  
Programmed Death ◽  
Monoclonal Antibody Treatment ◽  
New Research

In recent years, the research achievements of immunotherapy were outstanding, especially in the field of cancer treatment. At present, the major breakthroughs have been made in the research of immunotherapy based on programmed death receptor 1 (programmed death 1, PD-1) or programmed death ligand 1 (programmed death-ligand 1, PD-L1) immune checkpoint blockage. The successful application of anti-PD-1/PD-L1 mono clonal antibody in various clinical trials has showed its remarkable potential in caner immunotherapy. However, the results were not always satisfactory that treatment results often show large individual differences between patients, and it’s usually only a small part of patients would respond the treatment. Thus, combination therapy has become a new research focus in anti-PD-1/PD-L1 blockage-based therapy strategy development. This article will review the combination strategies of anti-PD-1/PD-L1 mAbs treatment and discuss the development and the trend of combination immunotherapy.

scholarly journals A critical role for the programmed death ligand 1 in fetomaternal tolerance

2005 ◽  
Vol 202 (2) ◽  
pp. 231-237 ◽  
Author(s):  
Indira Guleria ◽  
Arezou Khosroshahi ◽  
Mohammed Javeed Ansari ◽  
Antje Habicht ◽  
Miyuki Azuma ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Critical Role ◽  
Costimulatory Molecule ◽  
Antibody Treatment ◽  
Programmed Death Ligand 1 ◽  
Fetal Survival ◽  
Programmed Death ◽  
Ifn Γ ◽  
Rag 1

Fetal survival during gestation implies that tolerance mechanisms suppress the maternal immune response to paternally inherited alloantigens. Here we show that the inhibitory T cell costimulatory molecule, programmed death ligand 1 (PDL1), has an important role in conferring fetomaternal tolerance in an allogeneic pregnancy model. Blockade of PDL1 signaling during murine pregnancy resulted in increased rejection rates of allogeneic concepti but not syngeneic concepti. Fetal rejection was T cell– but not B cell–dependent because PDL1-specific antibody treatment caused fetal rejection in B cell–deficient but not in RAG-1–deficient females. Blockade of PDL1 also resulted in a significant increase in the frequency of IFN-γ–producing lymphocytes in response to alloantigen in an ELISPOT assay and higher IFN-γ levels in placental homogenates by ELISA. Finally, PDL1-deficient females exhibited decreased allogeneic fetal survival rates as compared with littermate and heterozygote controls and showed evidence of expansion of T helper type 1 immune responses in vivo. These results provide the first evidence that PDL1 is involved in fetomaternal tolerance.

scholarly journals Development of cancer immunotherapy based on PD-1/PD-L1 pathway blockade

RSC Advances ◽  
2019 ◽  
Vol 9 (58) ◽  
pp. 33903-33911 ◽  
Author(s):  
Min Zhang ◽  
Kehai Liu ◽  
Mingfu Wang
Keyword(s):  
Side Effects ◽  
Cancer Immunotherapy ◽  
Response Rate ◽  
Death Receptor ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

The possible reasons that caused low response rate and severe side effects of programmed death receptor 1 (PD-1)/programmed death ligand 1 (PD-L1) blockade therapy and corresponding strategies.

scholarly journals Programmed Death Ligand-1 Immunohistochemistry: Friend or Foe?

2016 ◽  
Vol 140 (4) ◽  
pp. 326-331 ◽  
Author(s):  
Keith M. Kerr ◽  
Fred R. Hirsch
Keyword(s):  
Lung Cancer ◽  
Death Receptor ◽  
Cancer Therapeutics ◽  
Predictive Biomarker ◽  
Small Cell ◽  
Small Cell Lung ◽  
Treatment Area ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Biomarker Testing

The approval of anti-programmed death receptor (PD)-1 therapies for non–small cell lung cancer has directed the spotlight on programmed death ligand-1 (PD-L1) immunohistochemistry as the latest predictive biomarker potentially required in this disease. Several other drugs in this class will likely be approved in the future and each has been developed with a unique anti–PD-L1 immunohistochemistry test. The prospect of 5 drugs competing in the same treatment area, each possibly requiring PD-L1 immunohistochemistry testing, presents a challenge for pathologists unlike any previously faced. The key issue is whether laboratories will attempt to deliver the trial-validated assays for one or more of these treatments, or introduce instead one or more laboratory developed tests, or attempt to provide a single PD-L1 immunohistochemistry assay for all possible anti–PD-1 and anti–PD-L1 treatments that may be used. This paper discusses some of the issues, challenges, hazards, and possible solutions that have recently emerged in this most complex interface between cancer therapeutics and laboratory biomarker testing.

scholarly journals Nivolumab-induced adrenalitis

2019 ◽  
Vol 12 (11) ◽  
pp. e231829 ◽  
Author(s):  
Iqra Iqbal ◽  
Muhammad Atique Alam Khan ◽  
Waqas Ullah ◽  
Dina Nabwani
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Small Cell ◽  
Second Line ◽  
Small Cell Lung ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Life Threatening ◽  
Line Chemotherapy

Immune checkpoint inhibitors (ICIs) are an evolving class of drugs for the treatment of various cancers; for example, their use is recommended as a second-line chemotherapy for non-small cell lung cancer. With the expanding use of ICIs, we are discovering their unique side effects, called immune-related adverse events (irAEs), which can impair gastrointestinal, hepatic, dermatological, endocrine and other systems. Nivolumab is an ICI that blocks the human programmed death receptor-1 (PD-1) on T cells to prevent the interaction between the receptor, PD-1, and human programmed death ligand-1 expressed on tumour cells. Here, we report a case of a 65-year-old woman with recurrent lung adenocarcinoma who was treated with nivolumab and developed immune-related adrenalitis, which was managed with hydrocortisone and fludrocortisone. This case highlights the importance of understanding the irAEs of ICIs to allow prompt recognition and management of life-threatening complications of the treatment.

scholarly journals Is There a Role for Programmed Death Ligand-1 Testing and Immunotherapy in Colorectal Cancer With Microsatellite Instability? Part II—The Challenge of Programmed Death Ligand-1 Testing and Its Role in Microsatellite Instability-High Colorectal Cancer

2017 ◽  
Vol 142 (1) ◽  
pp. 26-34 ◽  
Author(s):  
Esmeralda Celia Marginean ◽  
Barbara Melosky
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Microsatellite Instability ◽  
Therapeutic Potential ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Immune Checkpoints ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

Context.— The world of oncology has changed dramatically in the past few years with the introduction of checkpoint inhibitors and immunotherapy. The promising findings of a small, phase 2 clinical trial that led to the US Food and Drug Administration breakthrough designation and approval of the anti–programmed death receptor-1 (PD-1) drug pembrolizumab (Keytruda, Merck, Kenilworth, New Jersey) to treat metastatic/refractory microsatellite instability–high colorectal cancer (CRC) has significantly boosted interest in immunomodulatory therapies in microsatellite instability–high CRC. Objectives.— To review the immune response to cancer and the role of immune checkpoints, focusing on the technical and interpretation challenges of PD-1/programmed death ligand-1 (PD-L1) testing by pathologists and the clinical implications of the test and the therapeutic potential of treating CRC with checkpoint inhibitors. Data Sources.— A PubMed review was performed of articles pertaining to CRC, microsatellite instability and mismatch repair systems, molecular classification, immune response, PD-1/PD-L1, and immunotherapy. Conclusions.— Exciting success with anti–PD-1/PD-L1 and anticytotoxic T-lymphocyte–associated protein 4 (CTLA4) checkpoint inhibitors has already been reported in melanoma and in lung and renal carcinomas. Recently, microsatellite instability–high CRCs, expressing PD-L1 by immunohistochemistry, regardless of the level of that PD-L1 expression, appeared to respond to checkpoint blockades with anti–PD-1 or anti–PD-L1 agents, whereas microsatellite-stable tumors were much less responsive. With microsatellite instability routinely tested by most centers, studies that include larger cohorts are required to study the predictive role of PD-1/PD-L1 expression in microsatellite instability–high CRC, to assess which immunohistochemistry antibodies to use, to refine the scoring criteria, and to critically analyze the interpretation pitfalls.

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