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Immunotherapy ctla-4

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https://www.readbyqxmd.com/read/28335888/second-and-third-generation-drugs-for-immuno-oncology-treatment-the-more-the-better
#1
REVIEW
Wolfram C M Dempke, Klaus Fenchel, Peter Uciechowski, Stephen P Dale
Recent success in cancer immunotherapy (anti-CTLA-4, anti-PD1/PD-L1) has confirmed the hypothesis that the immune system can control many cancers across various histologies, in some cases producing durable responses in a way not seen with many small-molecule drugs. However, only less than 25% of all patients do respond to immuno-oncology drugs and several resistance mechanisms have been identified (e.g. T-cell exhaustion, overexpression of caspase-8 and β-catenin, PD-1/PD-L1 gene amplification, MHC-I/II mutations)...
March 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28325255/mucosal-melanoma-of-the-head-and-neck
#2
REVIEW
Paolo Antonio Ascierto, Remo Accorona, Gerardo Botti, Davide Farina, Piero Fossati, Gemma Gatta, Helen Gogas, Davide Lombardi, Roberto Maroldi, Piero Nicolai, Marco Ravanelli, Vito Vanella
Mucosal melanoma of the head and neck is a very rare and aggressive malignancy with a very poor prognosis. The nasal cavity, paranasal sinuses, and oral cavity are the most common locations. One-, 3- and 5-year survival rates between 2000 and 2007 were 63%, 30% and 20%, respectively. Cigarette smoking seems to be a risk factor even though the evidence for this is very low. Clinical signs and symptoms are usually nonspecific. While surgery is considered the mainstay of treatment for most mucosal melanomas of the head and neck region, radiotherapy has a role in local control of the disease after surgery...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28323141/mechanistic-and-pharmacologic-insights-on-immune-checkpoint-inhibitors
#3
REVIEW
Randy F Sweis, Jason J Luke
The concept of augmenting the immune system to eradicate cancer dates back at least a century. A major resurgence in cancer immunotherapy has occurred over the past decade since the identification and targeting of negative regulators with antibody therapies to augment the anti-tumor immune response. Unprecedented responses across a broad array of cancer types elevated this class of therapies to the forefront of cancer treatment. The most successful drugs to date target the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) pathways...
March 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28321814/immunotherapy-in-nsclc-a-promising-and-revolutionary-weapon
#4
Christian Rolfo, Christian Caglevic, Mariacarmela Santarpia, Antonio Araujo, Elisa Giovannetti, Carolina Diaz Gallardo, Patrick Pauwels, Mauricio Mahave
Lung cancer is the leader malignancy worldwide accounting 1.5 millions of deaths every year. In the United States the 5 year-overall survival is less than 20% for all the newly diagnosed patients. Cisplatin-based cytotoxic chemotherapy for unresectable or metastatic NSCLC patients in the first line of treatment, and docetaxel in the second line, have achieved positive results but with limited benefit in overall survival. Targeted therapies for EGFR and ALK mutant patients have showed better results when compared with chemotherapy, nevertheless most of patients will fail and need to be treated with chemotherapy if they still have a good performance status...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28318492/-brain-tumor-immunotherapy-illusion-or-hope
#5
REVIEW
Denis Migliorini, Valérie Dutoit, Paul R Walker, Pierre-Yves Dietrich
Immunotherapy has proven efficient for many tumors and is now part of standard of care in many indications. What is the picture for brain tumors? The recent development of anti-CTLA-4 and PD1 immune checkpoint inhibitors, which have the ability to restore T lymphocytes activity, has gathered enthusiasm and is now paving the way towards more complex models of immune system manipulation. These models include, among others, vaccination and adoptive T cell transfer technologies. Complementary to those strategies, molecules capable of reshaping the immune tumor microenvironment are currently being investigated in early phase trials...
March 16, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28318336/are-tumor-infiltrating-lymphocytes-protagonists-or-background-actors-in-patient-selection-for-cancer-immunotherapy
#6
Federica Zito Marino, Paolo Antonio Ascierto, Giulio Rossi, Stefania Staibano, Marco Montella, Daniela Russo, Roberto Alfano, Alessandro Morabito, Gerardo Botti, Renato Franco
Tumor-infiltrating lymphocytes (TILs) are frequently observed in several tumors, reflecting the dynamic process of ''cancer immunoediting''. Prognostic and predictive values of TILs have been demonstrated in different cancers, proving their pivotal role in clinical outcome. In recent years, new therapies targeting immune checkpoint inhibitors, especially CTLA-4 and PD-1/PDL-1 pathways, have been introduced into clinical practice. In this context, TILs may even have a possible utility as a predictive biomarker for immunotherapy response...
March 20, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28306559/immunotherapy-a-new-treatment-paradigm-in-bladder-cancer
#7
Nicole N Davarpanah, Akira Yuno, Jane B Trepel, Andrea B Apolo
PURPOSE OF REVIEW: T-cell checkpoint blockade has become a dynamic immunotherapy for bladder cancer. In 2016, atezolizumab, an immune checkpoint inhibitor, became the first new drug approved in metastatic urothelial carcinoma (mUC) in over 30 years. In 2017, nivolumab was also approved for the same indication. This overview of checkpoint inhibitors in clinical trials focuses on novel immunotherapy combinations, predictive biomarkers including mutational load and neoantigen identification, and an evaluation of the future of bladder cancer immunotherapy...
March 16, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28303311/-immunotherapy-of-cancer-with-checkpoint-inhibitors-not-only-in-malignant-melanoma
#8
A Neubauer
The newest weapon in cancer therapy is checkpoint inhibition, which is the result of basic immunology research. The success of this therapy is based on the fact that upon light microscopy, many solid tumors harbor lymphocytic cells infiltrating the tumor (TILs), and in many solid tumors, the presence of these TILs are prognostic. Ipilimumab was the first monoclonal antibody developed against a target present on T cells after becoming activated, CTLA-4. In malignant melanoma, ipilimumab showed its beneficial effect as compared to a placebo peptide...
March 16, 2017: Der Internist
https://www.readbyqxmd.com/read/28300768/tim-3-as-a-target-for-cancer-immunotherapy-and-mechanisms-of-action
#9
REVIEW
Wenwen Du, Min Yang, Abbey Turner, Chunling Xu, Robert L Ferris, Jianan Huang, Lawrence P Kane, Binfeng Lu
Cancer immunotherapy has produced impressive clinical results in recent years. Despite the success of the checkpoint blockade strategies targeting cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death receptor 1 (PD-1), a large portion of cancer patients have not yet benefited from this novel therapy. T cell immunoglobulin and mucin domain 3 (TIM-3) has been shown to mediate immune tolerance in mouse models of infectious diseases, alloimmunity, autoimmunity, and tumor Immunity. Thus, targeting TIM-3 emerges as a promising approach for further improvement of current immunotherapy...
March 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28300714/biomarkers-and-immunotherapeutic-targets-in-glioblastoma
#10
REVIEW
Alice L Hung, Tomas Garzon-Muvdi, Michael Lim
Glioblastoma (GBM) is an aggressive central nervous system (CNS) cancer with poor prognosis despite maximal therapy. The recent advent of immunotherapy holds great promise for improving GBM survival and has already made great strides towards changing current management strategies. A diverse set of biomarkers has been implicated as immunotherapeutic targets and prognostic indicators in other cancers. Some of the more extensively studied examples include cytokines (IL-4, IL-13, and TGF-ß), checkpoint molecules (PD-1, CTLA-4, TIM-3, LAG-3, CD137, GITR, OX40), and growth/angiogenesis proteins (endoglin and EGFR)...
March 11, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28296676/histopathologic-features-of-colitis-due-to-immunotherapy-with-anti-pd-1-antibodies
#11
Jonathan H Chen, Maryam K Pezhouh, Gregory Y Lauwers, Ricard Masia
Programmed cell death protein 1 (PD-1) blocking agents are novel immunotherapeutics used for treatment of advanced-stage malignancies. They have shown promise in the treatment of several malignancies, with greater efficacy and better tolerability than cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking agents. However, as with anti-CTLA-4 agents, clinically significant colitis remains an important complication. Although there is growing awareness of the histopathologic features of anti-CTLA-4 therapy, there is little information on the pathologic features of anti-PD-1 colitis...
March 14, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28289089/molecular-pathways-oncologic-pathways-and-their-role-in-t-cell-exclusion-and-immune-evasion-a-new-role-for-the-axl-receptor-tyrosine-kinase
#12
Todd A Aguilera, Amato J Giaccia
With the clinical impact of CTLA-4 and PD-1/PD-L1 immune checkpoint therapies, widespread interest in cancer immunotherapy has been ignited. However, the rate and extent of clinical responses to approved therapies are limited and often non-existent in many solid tumors. This is partially because immune checkpoint therapies are most effective against T-cell inflamed tumors, and non-T-cell inflamed or T-cell excluded tumors remain a significant barrier. New strategies are needed to overcome immune resistance mechanisms that arise during tumor development which result in T-cell exclusion...
March 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28287848/immunomodulating-and-immunoresistance-properties-of-cancer-initiating-cells-implications-for-the-clinical-success-of-immunotherapy
#13
Cristina Maccalli, Giorgio Parmiani, Soldano Ferrone
Cancer-initiating cells (CICs) represent a relatively rare subpopulation of cells endowed with self-renewal, stemness properties, tumorigenicity in immunodeficient mice, and resistance to standard therapies as well as to immunotherapy. Here, we review the biological and immunological characteristics of CICs with special focus on the immunomodulating mechanisms they utilize to escape from immunosurveillance. The recently developed immunotherapeutic strategies have yielded remarkable clinical results in many types of tumors, indicating that indeed a patient's immune system can mount an immune response, which is effective in controlling tumor growth...
March 13, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28286286/cancer-immunotherapy-targeting-the-cd47-sirp%C3%AE-axis
#14
REVIEW
Kipp Weiskopf
The success of cancer immunotherapy has generated tremendous interest in identifying new immunotherapeutic targets. To date, the majority of therapies have focussed on stimulating the adaptive immune system to attack cancer, including agents targeting CTLA-4 and the PD-1/PD-L1 axis. However, macrophages and other myeloid immune cells offer much promise as effectors of cancer immunotherapy. The CD47/signal regulatory protein alpha (SIRPα) axis is a critical regulator of myeloid cell activation and serves a broader role as a myeloid-specific immune checkpoint...
March 9, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28275910/mechanisms-of-drug-resistance-in-melanoma
#15
Matthew Winder, Amaya Virós
Metastatic melanoma is associated with poor outcome and is largely refractory to the historic standard of care. In recent years, the development of targeted small-molecule inhibitors and immunotherapy has revolutionised the care and improved the overall survival of these patients. Therapies targeting BRAF and MEK to block the mitogen-activated protein kinase (MAPK) pathway were the first to show unprecedented clinical responses. Following these encouraging results, antibodies targeting immune checkpoint inhibition molecules cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death (PD)-1, and PD-ligand1(PD-L1) demonstrated sustained tumour regression in a significant subset of patients by enabling an anti-tumour immunologic response...
March 9, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28258699/new-checkpoints-in-cancer-immunotherapy
#16
REVIEW
Ling Ni, Chen Dong
Immune responses must be fine-tuned to allow effective clearance of invading pathogens, while maintain tolerance to self-antigens. T cells are the major effector cells for fighting and killing tumor cells. Immune checkpoints play a pivotal role in T cell activation, and determine the functional outcome of T cell receptor (TCR) signaling. The blockade of immune checkpoints CTLA-4 and PD-1 has already been one of the most successful cancer immunotherapies. In this review, we will focus on three novel inhibitory B7 family checkpoint molecules, B7-H3, B7S1 and VISTA...
March 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28258697/tim-3-and-its-role-in-regulating-anti-tumor-immunity
#17
REVIEW
Madhumita Das, Chen Zhu, Vijay K Kuchroo
Immunotherapy is being increasingly recognized as a key therapeutic modality to treat cancer and represents one of the most exciting treatments for the disease. Fighting cancer with immunotherapy has revolutionized treatment for some patients and therapies targeting the immune checkpoint molecules such as CTLA-4 and PD-1 have achieved durable responses in melanoma, renal cancer, Hodgkin's diseases and lung cancer. However, the success rate of these treatments has been low and a large number of cancers, including colorectal cancer remain largely refractory to CTLA-4 and PD-1 blockade...
March 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28258695/tigit-and-cd96-new-checkpoint-receptor-targets-for-cancer-immunotherapy
#18
REVIEW
William C Dougall, Sema Kurtulus, Mark J Smyth, Ana C Anderson
While therapies targeting the co-inhibitory or immune checkpoint receptors PD-1 and CTLA-4 have shown remarkable success in many cancers, not all patients benefit from these therapies. This has catalyzed enormous interest in the targeting of other immune checkpoint receptors. In this regard, TIGIT and CD96 have recently entered the limelight as novel immune checkpoint receptor targets. TIGIT and CD96 together with the co-stimulatory receptor CD226 form a pathway that is analogous to the CD28/CTLA-4 pathway, in which shared ligands and differential receptor:ligand affinities fine-tune the immune response...
March 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28256019/ipilimumab-has-efficacy-in-metastatic-merkel-cell-carcinoma-a-case-series-of-five-patients
#19
J K Winkler, A Dimitrakopoulou-Strauss, C Sachpekidis, A Enk, J C Hassel
Immunotherapy with immune checkpoint blockers such as the CTLA-4 antibody ipilimumab and PD-1 antibodies has revolutionized oncological treatment options(1) . MCC is an immunogenic tumor and the efficacy of PD-1 blockade has recently been demonstrated(2,3,4) . Here, we present a retrospective analysis of five patients with metastatic MCC individually treated with ipilimumab between 2012 and 2015. Administration of four cycles (3 mg/kg every three weeks) was planned. Informed consent was obtained from all patients...
March 3, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28246107/comprehensive-meta-analysis-of-key-immune-related-adverse-events-from-ctla-4-and-pd-1-pd-l1-inhibitors-in-cancer-patients
#20
Guillermo De Velasco, Youjin Je, Dominick Bossé, Mark M Awad, Patrick A Ott, Raphael B Moreira, Fabio A B Schutz, Joaquim Bellmunt, Guru Sonpavde, F Stephen Hodi, Toni K Choueiri
Immune-related adverse events (irAEs) have been described with immune checkpoint inhibitors (ICIs), but the incidence and relative risk (RR) of irAEs associated with these drugs remains unclear. We selected five key irAEs from treatments with approved cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors (ipilimumab, nivolumab or pembrolizumab, and atezolizumab, respectively) to better characterize their safety profile. We performed a meta-analysis of randomized phase II/III immunotherapy trials, with non-ICI control arms, conducted between 1996 and 2016...
February 28, 2017: Cancer Immunology Research
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