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 A bi-adjuvant nanovaccine that potentiates immunogenicity of neoantigen for combination immunotherapy of colorectal cancer

2020 ◽  
Vol 6 (12) ◽  
pp. eaaw6071 ◽  
Author(s):  
Qianqian Ni ◽  
Fuwu Zhang ◽  
Yijing Liu ◽  
Zhantong Wang ◽  
Guocan Yu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Immunotherapy ◽  
Death Receptor ◽  
Therapy Response ◽  
Complete Regression ◽  
Combination Immunotherapy ◽  
Toll Like Receptor ◽  
Physical Loading ◽  
Programmed Death ◽  
Personalized Cancer

Neoantigen vaccines have been enthusiastically pursued for personalized cancer immunotherapy while vast majority of neoantigens have no or low immunogenicity. Here, a bi-adjuvant neoantigen nanovaccine (banNV) that codelivered a peptide neoantigen (Adpgk) with two adjuvants [Toll-like receptor (TLR) 7/8 agonist R848 and TLR9 agonist CpG] was developed for potent cancer immunotherapy. Specifically, banNVs were prepared by a nanotemplated synthesis of concatemer CpG, nanocondensation with cationic polypeptides, and then physical loading with hydrophobic R848 and Adpgk. The immunogenicity of the neoantigen was profoundly potentiated by efficient codelivery of neoantigen and dual synergistic adjuvants, which is accompanied by reduced acute systemic toxicity. BanNVs sensitized immune checkpoint programmed death receptor 1 (PD-1) on T cells, therefore, a combination of banNVs with aPD-1 conspicuously induced the therapy response and led to complete regression of 70% neoantigen-specific tumors without recurrence. We conclude that banNVs are promising to optimize personalized therapeutic neoantigen vaccines for cancer immunotherapy.

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 Trends in the Research Into Immune Checkpoint Blockade by Anti-PD1/PDL1 Antibodies in Cancer Immunotherapy: A Bibliometric Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Yiting Sun ◽  
Liqing Jiang ◽  
Ti Wen ◽  
Xiaoyu Guo ◽  
Xinye Shao ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Molecular Mechanisms ◽  
Randomized Clinical Trials ◽  
Tumor Regression ◽  
Meta Analysis ◽  
Death Receptor ◽  
Bibliometric Study ◽  
Immune Checkpoints ◽  
Knowledge Map ◽  
Programmed Death

The programmed death receptor 1 (PD1) and its ligand programmed death receptor ligand 1 (PDL1) are the most widely used immune checkpoints in cancer immunotherapy. The related literature shows the explosive growth trends due to the promising outcomes of tumor regression. The present study aimed to provide a comprehensive bibliometric analysis of the literature on anti-PD1/PDL1 from three perspectives including molecular mechanisms, randomized clinical trials (RCT), and meta-analysis, thus producing a knowledge map reflecting the status of the research, its historical evolution, and developmental trends in related research from 2000 to 2020. We included 11,971, 191, and 335 documents from the Web of Science Core Collection database, respectively, and adopted various bibliometric methods and techniques thereto. The study revealed the major research themes and emergent hotspots based on literature and citation data and outlined the top contributors in terms of journals and countries. The co-occurrence overlay of keywords and terms pertaining to the PD1/PDL1 molecule reflected the progress from the discovery of the PD1/PDL1 molecule to the clinical application of anti-PD1/PDL1. Immune-related adverse events (irAEs) formed a unique cluster in the term co-occurrence analysis of meta-analysis. The historical direct citation network of RCT indicated the development and transformation of cancers and therapy strategies. irAEs and the strategies of combination therapy might become a future focus of research in this cognate area. In summary, the bibliometric study provides a general overview of the landscape on anti-PD1/PDL1 research, allowing researchers to identify the potential opportunities and challenges therein.

scholarly journals Nivolumab for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma: Safety and Efficacy in the Phase II CheckMate 205 Study

2019 ◽  
Vol 37 (23) ◽  
pp. 1997-2007 ◽  
Author(s):  
Radhakrishnan Ramchandren ◽  
Eva Domingo-Domènech ◽  
Antonio Rueda ◽  
Marek Trněný ◽  
Tatyana A. Feldman ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Advanced Stage ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Programmed Death Ligand 1 ◽  
Classic Hodgkin Lymphoma ◽  
Immune Mediated ◽  
Programmed Death

PURPOSE Nivolumab, an anti–programmed death-1 monoclonal antibody, has demonstrated frequent and durable responses in relapsed/refractory classic Hodgkin lymphoma (cHL). We report results from Cohort D of the CheckMate 205 trial, which assessed nivolumab monotherapy followed by nivolumab plus doxorubicin, vinblastine, and dacarbazine (N-AVD) for newly diagnosed cHL. METHODS Patients 18 years of age or older with untreated, advanced-stage (defined as III to IV and IIB with unfavorable risk factors) cHL were eligible for Cohort D of this multicenter, noncomparative, phase II trial. Patients received nivolumab monotherapy for four doses, followed by 12 doses of N-AVD; all doses were every 2 weeks, and nivolumab was administered at 240 mg intravenously. The primary end point was safety. Efficacy end points included objective response rate and modified progression-free survival, defined as time to disease progression/relapse, death, or next therapy. Chromosome 9p24.1 alterations and programmed death-ligand 1 expression were assessed in Hodgkin Reed-Sternberg cells in evaluable patients. RESULTS A total of 51 patients were enrolled and treated. At diagnosis, 49% of patients had an International Prognostic Score of 3 or greater. Overall, 59% experienced a grade 3 to 4 treatment-related adverse event. Treatment-related febrile neutropenia was reported in 10% of patients. Endocrine immune-mediated adverse events were all grade 1 to 2 and did not require high-dose corticosteroids; all nonendocrine immune-mediated adverse events resolved (most commonly, rash; 5.9%). At the end of therapy, the objective response rate (95% CI) per independent radiology review committee was 84% (71% to 93%), with 67% (52% to 79%), achieving complete remission (five patients [10%] were nonevaluable and counted as nonresponders). With a minimum follow-up of 9.4 months, 9-month modified progression-free survival was 92%. Patients with higher-level Hodgkin Reed-Sternberg programmed death-ligand 1 expression had more favorable responses to N-AVD ( P = .041). CONCLUSION Nivolumab followed by N-AVD was associated with promising efficacy and safety profiles for newly diagnosed, advanced-stage cHL.

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 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.

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