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Immune checkpoint inhibitor

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https://www.readbyqxmd.com/read/28741518/companion-and-complementary-diagnostics-clinical-and-regulatory-perspectives
#1
REVIEW
Jan Trøst Jørgensen
Nearly 20 years ago, the US Food and Drug Administration (FDA) approved the first companion diagnostic assay and, today, this type of test governs the use of 18 different drugs. With the appearance of PD-L1 immunohistochemistry (IHC) assays linked to the use of different PD-1/PD-L1 immune checkpoint inhibitors, a new class of predictive biomarker assays has emerged; the complementary diagnostics. These are predictive biomarker assays that aid the therapeutic decision process but are not a prerequisite for receiving a specific drug, as is the case with companion diagnostics...
December 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28739315/combination-therapy-of-radiotherapy-and-anti-pd-1-pd-l1-treatment-in-non-small-cell-lung-cancer-a-mini-review
#2
REVIEW
Shinkichi Takamori, Gouji Toyokawa, Kazuki Takada, Fumihiro Shoji, Tatsuro Okamoto, Yoshihiko Maehara
Immune checkpoint inhibitors against programmed cell death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) are a standard pharmacologic therapy for patients with non-small-cell lung cancer (NSCLC). Substantial data have accumulated in recent years showing that radiotherapy combined with immunotherapy is more effective than monotherapy alone. Preclinical studies have shown that PD-L1 expression is upregulated on tumor cells after radiotherapy, resulting in the synergistically enhanced antitumor effect of irradiation and PD-L1 blockade...
July 6, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28737620/sarcoidosis-following-anti-pd-1-and-anti-ctla-4-therapy-for-metastatic-melanoma
#3
Swathi B Reddy, Jennifer D Possick, Harriet M Kluger, Anjela Galan, Dale Han
Immune checkpoint inhibitors represent the newest treatment for stage IV melanoma. These agents are generally well tolerated, however severe immune-related adverse effects have been noted in a small, but clinically significant percentage of patients. Specifically, sarcoidosis is a known potential complication following anti-CTLA-4 therapy. We present 2 cases of pulmonary and cutaneous sarcoidosis developing in patients with stage IV melanoma. Both patients were treated with ipilimumab and anti-PD-1 therapy, and both experienced good oncologic responses to treatment; neither had evidence of preexisting sarcoidosis...
July 21, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28737430/nivolumab-for-the-treatment-of-bladder-cancer
#4
Oliver W Hakenberg
The checkpoint inhibitor nivolumab has recently demonstrated effectiveness against metatstatic urothelial carcinoma. Nivolumab is a fully human monoclonal antibody blocking PD-1 and thereby enhancing antitumour immune mechanisms. Areas covered: In this review, the authors describe the treatment of metastatic bladder cancer with nivolumab against the background of the standard treatment with cisplatin-based chemotherapy which can prolong overall survival from 3-6 months in untreated cases to over one year. Different combinations of cisplatin-based chemotherapy can further prolong survival by only a few months...
July 24, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28736633/biologics-in-gastrointestinal-and-pancreatic-neuroendocrine-tumors
#5
REVIEW
Iris H Liu, Pamela L Kunz
The development of biologic agents has ushered in a new era of precision medicine, opening the door to new therapeutic options designed to intelligently target cancer cells and their promoting factors, while leaving normal cells relatively unharmed. Biologics for the treatment of neuroendocrine tumors (NETs) have followed in the footsteps of regimens targeting pathways upregulated in other cancers, including the vascular endothelial growth factor (VEGF) and the mammalian target of rapamycin (mTOR). Through a number of clinical trials, the mTOR inhibitor everolimus and the receptor tyrosine kinase (RTK) inhibitor sunitinib were recently approved for NETs...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28734759/nivolumab-in-patients-with-metastatic-dna-mismatch-repair-deficient-or-microsatellite-instability-high-colorectal-cancer-checkmate-142-an-open-label-multicentre-phase-2-study
#6
Michael J Overman, Ray McDermott, Joseph L Leach, Sara Lonardi, Heinz-Josef Lenz, Michael A Morse, Jayesh Desai, Andrew Hill, Michael Axelson, Rebecca A Moss, Monica V Goldberg, Z Alexander Cao, Jean-Marie Ledeine, Gregory A Maglinte, Scott Kopetz, Thierry André
BACKGROUND: Metastatic DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer has a poor prognosis after treatment with conventional chemotherapy and exhibits high levels of tumour neoantigens, tumour-infiltrating lymphocytes, and checkpoint regulators. All of these features are associated with the response to PD-1 blockade in other tumour types. Therefore, we aimed to study nivolumab, a PD-1 immune checkpoint inhibitor, in patients with dMMR/MSI-H metastatic colorectal cancer...
July 19, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28734176/cancer-immunotherapy-moving-forward-with-peptide-t-cell-vaccines
#7
REVIEW
Takumi Kumai, Aaron Fan, Yasuaki Harabuchi, Esteban Celis
Recent advances in cancer immunology, such as the discovery of immune checkpoint inhibitors, have validated immune cells as potential key players for effective cancer treatment. The efficacy of these therapies seems to be codependent on a tumor-reactive T lymphocyte response. For many years, numerous attempts and strategies in developing vaccines to generate tumor-reactive T cells have yielded poor results in the clinic due to suboptimal immunogenicity and the inability to overcome an immunosuppressive tumor microenvironment...
July 19, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28733892/comparison-of-recist-to-immune-related-response-criteria-in-patients-with-non-small-cell-lung-cancer-treated-with-immune-checkpoint-inhibitors
#8
Hee Kyung Kim, Mi Hwa Heo, Han Sang Lee, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
PURPOSE: Given that immune-related response in non-small cell lung cancer (NSCLC) has not been well evaluated, we assessed tumor response using the response evaluation criteria in solid tumors, version 1.1 (RECIST v1.1) and immune-related response criteria (irRC) to identify atypical responses in patients with advanced NSCLC treated with immunotherapeutic agents. METHODS: Patients received immune-checkpoint inhibitors (pembrolizumab, atezolizumab, nivolumab, and durvalumab plus tremelimumab) to treat metastatic or recurrent NSCLC after failed platinum-based chemotherapy...
July 21, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28733704/-adverse-effects-of-immunotherapy-clinical-aspects-radiological-and-nuclear-medicine-results
#9
REVIEW
G Widmann, V A Nguyen, J Plaickner, W Jaschke
BACKGROUND: The increasing use of immunotherapy in oncology increases the need for radiologic evaluation of frequent and severe immune-related adverse events. OBJECTIVE: Determination of the incidence and manifestation of radiologic and nuclear medicine findings of immune-related adverse events. MATERIAL AND METHODS: Literature review of clinical and imaging findings of immune-related adverse events induced by the immune checkpoint inhibitors ipilimumab, nivolumab and pembrolizumab...
July 21, 2017: Der Radiologe
https://www.readbyqxmd.com/read/28732118/pd-1-checkpoint-blockade-in-combination-with-an-mtor-inhibitor-restrains-hepatocellular-carcinoma-growth-induced-by-hepatoma-cell-intrinsic-pd-1
#10
Hui Li, Xiaoqiang Li, Shuang Liu, Lei Guo, Bo Zhang, Jubo Zhang, Qinghai Ye
Inhibitors of PD-1 administered as single agents have resulted in durable tumor regression in advanced cancer patients. However, only a minority of cancer patients respond to anti PD-1 immunotherapy. Here, we show that PD-1 expression in hepatocellular carcinoma (HCC) promotes tumor growth independently of adaptive immunity. Knockdown of PD-1 suppress tumor growth, whereas PD-1 overexpression enhances tumorigenesis in immunodeficient xenografted mice. Mechanistically, PD-1 binds the downstream mTOR effectors eukaryotic initiation factor 4E (eIF4E) and ribosomal protein S6 (S6), thus promoting their phosphorylation...
July 21, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28731944/cancer-immunotherapy-in-older-patients
#11
Kristen A Marrone, Patrick M Forde
Advancing age remains one of the most significant risk factors for cancer development. Changes in the immune system occur with aging, and likely play a role in the increased incidence of malignancy in older patients. With the advent of immune checkpoint inhibitors, and their use in a variety of malignancies, there has been an explosion of clinical trials evaluating their use. Unfortunately, these trials have not shown consistent results in elderly patients, nor have age-specific outcomes been consistently reported...
July 2017: Cancer Journal
https://www.readbyqxmd.com/read/28730537/lung-cancer-as-a-paradigm-for-precision-oncology-in-solid-tumours
#12
Simon Schallenberg, Sabine Merkelbach-Bruse, Reinhard Buettner
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the western world. However, the combination of molecular genotyping and subsequent systematic treatment of decoded target structures is a prime example of precision oncology in solid tumours. In this review, current targets of approved therapeutics and potential targets in clinical and preclinical trials are outlined. Furthermore, immune checkpoint inhibitors, as promising new therapeutic options, which have already been applied successfully in cases of lung cancer, are introduced...
July 20, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28730266/-malignant-melanoma-current-status
#13
REVIEW
J K Winkler, K Buder-Bakhaya, A Dimitrakopoulou-Strauss, A Enk, J C Hassel
CLINICAL ISSUE: The incidence of malignant melanoma is continuously increasing. The prognosis of metastatic disease is still limited. STANDARD TREATMENT: Until a few years ago palliative chemotherapy with a limited response rate was the standard treatment for metastatic melanoma. TREATMENT INNOVATIONS: Immunotherapy and targeted therapy provide new treatment options. Immune checkpoint inhibitors have significantly improved the prognosis. DIAGNOSTIC WORK-UP: Regional lymph node sonography, computed tomography (CT) of the neck, chest and abdomen and brain magnetic resonance imaging (MRI) are routinely used...
July 20, 2017: Der Radiologe
https://www.readbyqxmd.com/read/28730140/current-advances-in-checkpoint-inhibitors-lessons-from-non-central-nervous-system-cancers-and-potential-for-glioblastoma
#14
REVIEW
Natasha Lakin, Robert Rulach, Stefan Nowicki, Kathreena M Kurian
The adaptive immune system depends on the sequence of antigen presentation, activation, and then inhibition to mount a proportionate response to a threat. Tumors evade the immune response partly by suppressing T-cell activity using immune checkpoints. The use of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1) antibodies counteract this suppression, thereby enhancing the antitumor activity of the immune system. This approach has proven efficacy in melanoma, renal cancer, and lung cancer...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28729358/targeting-c-type-lectin-receptors-a-high-carbohydrate-diet-for-dendritic-cells-to-improve-cancer-vaccines
#15
REVIEW
Dieke van Dinther, Dorian A Stolk, Rieneke van de Ven, Yvette van Kooyk, Tanja D de Gruijl, Joke M M den Haan
There is a growing understanding of why certain patients do or do not respond to checkpoint inhibition therapy. This opens new opportunities to reconsider and redevelop vaccine strategies to prime an anticancer immune response. Combination of such vaccines with checkpoint inhibitors will both provide the fuel and release the brake for an efficient anticancer response. Here, we discuss vaccine strategies that use C-type lectin receptor (CLR) targeting of APCs, such as dendritic cells and macrophages. APCs are a necessity for the priming of antigen-specific cytotoxic and helper T cells...
July 20, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28729151/standard-dose-pembrolizumab-in-combination-with-reduced-dose-ipilimumab-for-patients-with-advanced-melanoma-keynote-029-an-open-label-phase-1b-trial
#16
Georgina V Long, Victoria Atkinson, Jonathan S Cebon, Michael B Jameson, Bernie M Fitzharris, Catriona M McNeil, Andrew G Hill, Antoni Ribas, Michael B Atkins, John A Thompson, Wen-Jen Hwu, F Stephen Hodi, Alexander M Menzies, Alexander D Guminski, Richard Kefford, Benjamin Y Kong, Babak Tamjid, Archana Srivastava, Anna J Lomax, Mohammed Islam, Xinxin Shu, Scot Ebbinghaus, Nageatte Ibrahim, Matteo S Carlino
BACKGROUND: Reduced-dose nivolumab in combination with standard-dose ipilimumab improves objective response and progression-free survival compared with standard-dose ipilimumab alone, but increases toxicity. We assessed the safety and anti-tumour activity of standard-dose pembrolizumab in combination with reduced-dose ipilimumab. METHODS: In this open-label, phase 1b trial, we recruited patients from 12 medical centres in Australia, New Zealand, and the USA. Eligible patients were aged at least 18 years, had advanced melanoma, had an Eastern Coooperative Oncology Group performance status of 0 or 1, had measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1...
July 17, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28728794/myeloid-suppressor-cells-in-cancer-and-autoimmunity
#17
REVIEW
Antonio Sica, Marco Massarotti
A bottleneck for immunotherapy of cancer is the immunosuppressive microenvironment in which the tumor cells proliferate. Cancers harness the immune regulatory mechanism that prevents autoimmunity from evading immunosurveillance and promoting immune destruction. Regulatory T cells, myeloid suppressor cells, inhibitory cytokines and immune checkpoint receptors are the major components of the immune system acting in concert with cancer cells and causing the subversion of anti-tumor immunity. This redundant immunosuppressive network poses an impediment to efficacious immunotherapy by facilitating tumor progression...
July 17, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28725427/progressive-hypoventilation-due-to-mixed-cd8-and-cd4-lymphocytic-polymyositis-following-tremelimumab-durvalumab-treatment
#18
Sooraj John, Scott J Antonia, Trevor A Rose, Robert P Seifert, Barbara A Centeno, Aaron S Wagner, Ben C Creelan
BACKGROUND: The combination of CTLA-4 and PD-L1 inhibitors has a manageable adverse effect profile, although rare immune-related adverse events (irAE) can occur. CASE PRESENTATION: We describe an autoimmune polymyositis following a partial response to combination tremelimumab and durvalumab for the treatment of recurrent lung adenocarcinoma. Radiography revealed significant reduction in all metastases; however, the patient developed progressive neuromuscular hypoventilation due to lymphocytic destruction of the diaphragmatic musculature...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28724377/combination-therapy-for-melanoma-with-braf-mek-inhibitor-and-immune-checkpoint-inhibitor-a-mathematical-model
#19
Xiulan Lai, Avner Friedman
BACKGROUND: The B-raf gene is mutated in up to 66% of human malignant melanomas, and its protein product, BRAF kinase, is a key part of RAS-RAF-MEK-ERK (MAPK) pathway of cancer cell proliferation. BRAF-targeted therapy induces significant responses in the majority of patients, and the combination BRAF/MEK inhibitor enhances clinical efficacy, but the response to BRAF inhibitor and to BRAF/MEK inhibitor is short lived. On the other hand, treatment of melanoma with an immune checkpoint inhibitor, such as anti-PD-1, has lower response rate but the response is much more durable, lasting for years...
July 19, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28723666/increased-cflip-expression-in-thymic-epithelial-tumors-blocks-autophagy-via-nf-%C3%AE%C2%BAb-signalling
#20
Djeda Belharazem, Albert Grass, Cornelia Paul, Mario Vitacolonna, Berthold Schalke, Ralf J Rieker, Daniel Körner, Philipp Jungebluth, Katja Simon-Keller, Peter Hohenberger, Eric M Roessner, Karsten Wiebe, Thomas Gräter, Thomas Kyriss, German Ott, Peter Geserick, Martin Leverkus, Philipp Ströbel, Alexander Marx
The anti-apoptotic cellular FLICE-like inhibitory protein cFLIP plays a pivotal role in normal tissues homoeostasis and the development of many tumors, but its role in normal thymus (NT), thymomas and thymic carcinomas (TC) is largely unknown.Expression, regulation and function of cFLIP were analyzed in biopsies of NT, thymomas, thymic squamous cell carcinomas (TSCC), thymic epithelial cells (TECs) derived thereof and in the TC line 1889c by qRT-PCR, western blot, shRNA techniques, and functional assays addressing survival, senescence and autophagy...
February 6, 2017: Oncotarget
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