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https://www.readbyqxmd.com/read/29416316/durvalumab-an-investigational-anti-pd-l1-monoclonal-antibody-for-the-treatment-of-urothelial-carcinoma
#1
REVIEW
Izak Faiena, Amy L Cummings, Anna M Crosetti, Allan J Pantuck, Karim Chamie, Alexandra Drakaki
Our expanding knowledge of immunotherapy for solid tumors has led to an explosion of clinical trials aimed at urothelial carcinoma. The primary strategy is centered on unleashing the immune system by releasing the inhibitory signals propagated by programmed cell death-1 (PD-1) and its ligand programmed cell death ligand-1 (PD-L1). Many antibody constructs have been developed to block these interactions and are used in clinical trials. The Food and Drug Administration has already approved a number of checkpoint inhibitors such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) monoclonal antibodies including ipilimumab; anti-PD-1 monoclonal antibodies including nivolumab and pembrolizumab; anti-PD-L1 antibodies including atezolizumab, avelumab, and durvalumab...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29396294/pd-1-pdcd1-promoter-methylation-is-a-prognostic-factor-in-patients-with-diffuse-lower-grade-gliomas-harboring-isocitrate-dehydrogenase-idh-mutations
#2
Lea Kristin Röver, Heidrun Gevensleben, Jörn Dietrich, Friedrich Bootz, Jennifer Landsberg, Diane Goltz, Dimo Dietrich
Immune checkpoints are important targets for immunotherapies. However, knowledge on the epigenetic modification of immune checkpoint genes is sparse. In the present study, we investigated promoter methylation of CTLA4, PD-L1, PD-L2, and PD-1 in diffuse lower-grade gliomas (LGG) harboring isocitrate dehydrogenase (IDH) mutations with regard to mRNA expression levels, clinicopathological parameters, previously established methylation subtypes, immune cell infiltrates, and survival in a cohort of 419 patients with IDH-mutated LGG provided by The Cancer Genome Atlas...
January 24, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29385894/role-of-immune-checkpoint-inhibitors-in-lung-cancer
#3
Prantesh Jain, Chhavi Jain, Vamsidhar Velcheti
Immune checkpoint inhibitors, mainly drugs targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA4) pathways, represent a remarkable advance in lung cancer treatment. Immune checkpoint inhibitors targeting PD-1 and PD-L1 are approved for the treatment of patients with non-small-cell lung cancer, with impressive clinical activity and durable responses in some patients. This review will summarize the mechanism of action of these drugs, the clinical development of these agents and the current role of these agents in the management of patients with lung cancer...
January 2018: Therapeutic Advances in Respiratory Disease
https://www.readbyqxmd.com/read/29383037/interferon-gamma-an-important-marker-of-response-to-immune-checkpoint-blockade-in-non-small-cell-lung-cancer-and-melanoma-patients
#4
Niki Karachaliou, Maria Gonzalez-Cao, Guillermo Crespo, Ana Drozdowskyj, Erika Aldeguer, Ana Gimenez-Capitan, Cristina Teixido, Miguel Angel Molina-Vila, Santiago Viteri, Maria De Los Llanos Gil, Salvador Martin Algarra, Elisabeth Perez-Ruiz, Ivan Marquez-Rodas, Delvys Rodriguez-Abreu, Remedios Blanco, Teresa Puertolas, Maria Angeles Royo, Rafael Rosell
Background: Programmed death-ligand 1 (PD-L1) may be induced by oncogenic signals or can be upregulated via interferon gamma (IFN-γ). We have explored whether the expression of IFNG, the gene encoding IFN-γ, is associated with clinical response to the immune checkpoint blockade in non-small cell lung cancer (NSCLC) and melanoma patients. The role of inflammation-associated transcription factors STAT3, IKBKE, STAT1 and other associated genes has also been examined. Methods: Total RNA from 17 NSCLC and 21 melanoma patients was analyzed by quantitative reverse transcription PCR...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29381409/complete-ophthalmoplegia-in-ipilmumab-and-nivolumab-combination-treatment-for-metastatic-melanoma
#5
Reem Alnabulsi, Ahsen Hussain, Dan DeAngelis
Ipilimumab and Nivolumab are novel monoclonal antibodies that have recently been used successfully for treatment of metastatic melanoma. Ipilimumab is a human monoclonal antibody against Cytotoxic T Lymphocyte Antigen 4 (CTLA4) receptor, which suppresses T-cell proliferation and stimulates an inflammatory response against cancer cells. Nivolumab is an IgG4 monoclonal antibody against the cytotoxic T lymphocyte associated programmed death 1 receptor (PD-1). Ipilimumab and Nivolumab combination treatment has been shown to induce remission and prolong survival in patients with metastatic melanoma...
January 30, 2018: Orbit
https://www.readbyqxmd.com/read/29361059/t-cell-receptor-%C3%AE-recombinations-in-renal-cell-carcinoma-exome-files-correlate-with-an-intermediate-level-of-t-cell-exhaustion-biomarkers
#6
Anne T Mai, Wei Lue Tong, Yaping N Tu, George Blanck
Renal cell carcinoma exome-derived, V(D)J recombination reads had an elevated presence and variability, for both TcR-α and β, when compared to marginal tissue, reflecting an opportunity to assess tumor immunogenicity by comparison with marginal tissue T-cells. PD-1, PD-L2, CTLA4, and FOXP3, all of which are implicated in the evasion of an anti-tumor immune response, had a significantly higher expression for samples representing co-detection of productive TcR-⍺ and -β recombination reads. Samples representing tumors with productive TcR-α recombination reads but no detectable, productive TcR-β recombination reads, reflected a 20% survival advantage, and RNASeq data indicated an intermediate level of immune checkpoint gene expression for those samples...
January 18, 2018: International Immunology
https://www.readbyqxmd.com/read/29359792/pdcd1-and-ctla4-polymorphisms-affect-the-susceptibility-to-and-clinical-features-of-chronic-immune-thrombocytopenia
#7
Tetsuhiro Kasamatsu, Rumi Ino, Noriyuki Takahashi, Nanami Gotoh, Yusuke Minato, Makiko Takizawa, Akihiko Yokohama, Hiroshi Handa, Takayuki Saitoh, Norifumi Tsukamoto, Hirokazu Murakami
Programmed death-1 (PD-1, PDCD1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4, CTLA4) play central roles in immune checkpoint pathways. Single nucleotide polymorphisms (SNPs) of PDCD1 and CTLA4 have been reported to be associated with susceptibility to some autoimmune diseases. However, the potential association between SNPs in these immune checkpoint genes and risk of chronic immune thrombocytopenia (cITP) remain controversial and obscure. The aims of this study were to clarify the influence of PDCD1 and CTLA4 SNPs on the risk of developing cITP and its clinical features...
January 23, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29331646/progress-in-the-management-of-advanced-thoracic-malignancies-in-2017
#8
REVIEW
Roberto Ferrara, Laura Mezquita, Benjamin Besse
The treatment paradigm of non-small cell lung cancer (NSCLC) underwent a major revolution during the course of 2017. Immune checkpoint inhibitors (ICIs) brought remarkable improvements in response and overall survival (OS) both in unselected pretreated patients and in untreated patients with PD-L1 expression ≥50%. Furthermore, compelling preliminary results were reported for new combinations of anti-PD-1/PD-L1 agents with chemotherapy or anti-CTLA4 inhibitors. The success of the ICIs appeared to extend to patients with small cell lung cancer (SCLC), mesothelioma or thymic tumors...
January 10, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29319621/selective-cd28-inhibition-modulates-alloimmunity-and-cardiac-allograft-vasculopathy-in-anti-cd154-treated-monkeys
#9
Tianshu Zhang, Agnes M Azimzadeh, Wenji Sun, Natalie A O'Neill, Evelyn Sievert, Emily Bergbower, Gheorghe Braileanu, Lars Burdorf, Xiangfei Cheng, Thomas Monahan, Siamak Dahi, Donald Harris, Elana Rybak, Emily Welty, Anthony Kronfli, Chris Avon, Richard N Pierson
BACKGROUND: Selective CD28 inhibition is actively pursued as an alternative to B7 blockade using CTLA4-Ig based on the hypothesis that the checkpoint immune regulators CTLA-4 and PD-L1 will induce tolerogenic immune signals. We previously showed that blocking CD28 using a monovalent nonactivating reagent (single chain anti-CD28 Fv fragment linked to alpha-1 anti-trypsin: sc28AT) synergizes with calcineurin inhibitors in nonhuman primate (NHP) kidney and heart transplantation. Here, we explored the efficacy of combining a 3-week 'induction" sc28AT treatment with prolonged CD154 blockade...
January 10, 2018: Transplantation
https://www.readbyqxmd.com/read/29318609/the-efficacy-and-safety-of-anti-pd-1-pd-l1-antibodies-combined-with-chemotherapy-or-ctla4-antibody-as-a-first-line-treatment-for-advanced-lung-cancer
#10
Xiaoling Xu, Zhiyu Huang, Lei Zheng, Yun Fan
Checkpoint inhibitors show promising efficacy in advanced lung cancer, especially in non-small cell lung cancer. This meta-analysis was conducted to explore the therapeutic efficacy and safety of anti-PD-1/PD-L1 antibodies combined with chemotherapy or CTLA4 antibody as first-line treatments for patients with advanced lung cancer. A systematic search was performed in databases for this system review and quantitative meta-analysis. Twelve trials were finally enrolled in the meta-analysis. Our analyses revealed that the combined overall response rate (ORR) and disease control rate (DCR) for immune checkpoint inhibitors combined with chemotherapy for the treatment of non-small cell lung cancer (NSCLC) were 47...
January 10, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29318591/immune-checkpoint-molecules-in-acute-myeloid-leukaemia-managing-the-double-edged-sword
#11
REVIEW
Willemijn Hobo, Tim J A Hutten, Nicolaas P M Schaap, Harry Dolstra
New immunotherapeutic interventions have revolutionized cancer treatment. The immune responsiveness of acute myeloid leukaemia (AML) was first demonstrated by allogeneic stem cell transplantation. In addition, milder immunotherapeutic approaches are exploited. However, the long-term efficacy of these therapies is hampered by various immune resistance and editing mechanisms. In this regard, co-inhibitory signalling pathways have been shown to play a crucial role. Via up-regulation of inhibitory checkpoints, tumour-reactive T cell and Natural Killer cell responses can be strongly impeded...
January 9, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29283446/potential-cardiac-risk-of-immune-checkpoint-blockade-as-anticancer-treatment-what-we-know-what-we-do-not-know-and-what-we-can-do-to-prevent-adverse-effects
#12
REVIEW
Paolo Spallarossa, Giovanni Meliota, Claudio Brunelli, Eleonora Arboscello, Pietro Ameri, Christian Cadeddu Dessalvi, Francesco Grossi, Martino Deidda, Donato Mele, Matteo Sarocchi, Andrea Bellodi, Rosalinda Madonna, Giuseppe Mercuro
Cancer immunotherapy has become a well-established treatment option for some cancers after the development of a family of drugs targeting the so-called immune checkpoints, such as CTLA4 and PD-1 with PD-L1. These co-receptors/ligands inhibit the activation of T-cell, thus preventing an excessive inflammatory response. Tumors exploit these pathways to induce immune tolerance to themselves. Thus, the main effect of checkpoint-blocking drugs is to awake an immune response primarily directed against cancer cells...
December 28, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29279549/recent-progress-in-the-understanding-of-angioimmunoblastic-t-cell-lymphoma
#13
Manabu Fujisawa, Shigeru Chiba, Mamiko Sakata-Yanagimoto
Angioimmunoblastic T-cell lymphoma (AITL) has been classified as a subtype of mature T-cell neoplasms. The recent revision of the WHO classification proposed a new category of nodal T-cell lymphoma with follicular helper T (TFH)-cell phenotype, which was classified into three diseases: AITL, follicular T-cell lymphoma, and nodal peripheral T-cell lymphoma with TFH phenotype. These lymphomas are defined by the expression of TFH-related antigens, CD279/PD-1, CD10, BCL6, CXCL13, ICOS, SAP, and CXCR5. Although recurrent mutations in TET2, IDH2, DNMT3A, RHOA, and CD28, as well as gene fusions, such as ITK-SYK and CTLA4-CD28, were not diagnostic criteria, they may be considered as novel criteria in the near future...
2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/29250075/identification-and-characterization-of-neoantigens-as-well-as-respective-immune-responses-in-cancer-patients
#14
REVIEW
Eva Bräunlein, Angela M Krackhardt
Cancer immunotherapy has recently emerged as a powerful tool for the treatment of diverse advanced malignancies. In particular, therapeutic application of immune checkpoint modulators, such as anti-CTLA4 or anti-PD-1/PD-L1 antibodies, have shown efficacy in a broad range of malignant diseases. Although pharmacodynamics of these immune modulators are complex, recent studies strongly support the notion that altered peptide ligands presented on tumor cells representing neoantigens may play an essential role in tumor rejection by T cells activated by anti-CTLA4 and anti-PD-1 antibodies...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29233542/natural-killer-cells-and-anti-tumor-immunity
#15
Sandra E Nicholson, Narelle Keating, Gabrielle T Belz
Immune checkpoint inhibitors harness the power of the immune system to fight cancer. The clinical success achieved with antibodies against the inhibitory T cell receptors PD-1 and CTLA4 has focused attention on the possibility of manipulating other immune cells, in particular those involved in innate immunity. Here we review the role of innate lymphoid cells (ILCs) and their contribution to tumor immunity. As the prototypical ILC, the natural killer (NK) cell has an intrinsic ability to detect and kill cancer cells...
December 9, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29220526/anti-pd-l1-treatment-induced-central-diabetes-insipidus
#16
Chen Zhao, Sri Harsha Tella, Jaydira Del Rivero, Anuhya Kommalapati, Ifechukwude Ebenuwa, James Gulley, Julius Strauss, Isaac Brownell
Context: Immune checkpoint inhibitors, including anti-PD-1, anti-PD-L1 and anti-CTLA4 monoclonal antibodies, have been widely used in cancer treatment. They are known to cause immune-related adverse events (irAEs), which resemble autoimmune diseases. Anterior pituitary hypophysitis with secondary hypopituitarism is a frequently reported irAE, especially in patients receiving anti-CTLA4 treatment. In contrast, posterior pituitary involvement, such as central diabetes insipidus (DI), is relatively rare and is unreported in patients undergoing PD-1/PD-L1 blockade...
December 6, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29209572/trial-watch-immunostimulatory-monoclonal-antibodies-for-oncological-indications
#17
REVIEW
Mariona Cabo, Rienk Offringa, Laurence Zitvogel, Guido Kroemer, Aura Muntasell, Lorenzo Galluzzi
The goal of cancer immunotherapy is to establish new or boost pre-existing anticancer immune responses that eradicate malignant cells while generating immunological memory to prevent disease relapse. Over the past few years, immunomodulatory monoclonal antibodies (mAbs) that block co-inhibitory receptors on immune effectors cells - such as cytotoxic T lymphocyte-associated protein 4 (CTLA4), programmed cell death 1 (PDCD1, best known as PD-1) - or their ligands - such as CD274 (best known as PD-L1) - have proven very successful in this sense...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29206680/immune-therapies-in-acute-myeloid-leukemia-a-focus-on-monoclonal-antibodies-and-immune-checkpoint-inhibitors
#18
Rita Assi, Hagop Kantarjian, Farhad Ravandi, Naval Daver
PURPOSE OF REVIEW: This review discusses the rationale, efficacy, and toxicity of a variety of immune approaches being evaluated in the therapy of acute myeloid leukemia (AML) including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, and immune checkpoint blockade via antibodies targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed-death 1 (PD-1). RECENT FINDINGS: The stellar success of immune therapies that harness the power of T cells in solid tumors and an improved understanding of the immune system in patients with hematologic malignancies have resulted in major efforts to develop immune therapies for the treatment of patients with AML...
December 4, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29176936/role-of-microrna-33a-in-regulating-the-expression-of-pd-1-in-lung-adenocarcinoma
#19
Laura Boldrini, Mirella Giordano, Cristina Niccoli, Franca Melfi, Marco Lucchi, Alfredo Mussi, Gabriella Fontanini
Background: MiRNAs are vital in functioning as either oncogenes or tumor suppressors in the cell cycle. Target transcripts for immune checkpoint molecules such as PD-1/PD-L1 and (programmed cell death-1/its ligand and cytotoxic T-lymphocyte antigen 4) have proven to be beneficial against several solid tumors, including lung adenocarcinoma. Methods: Simultaneous quantification of the expression level of miR-33a and PD-1, PD-L1 and CTLA4 mRNAs with NanoString technology was performed in 88 lung adenocarcinoma specimens...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/29147629/trial-watch-immune-checkpoint-blockers-for-cancer-therapy
#20
REVIEW
Claire Vanpouille-Box, Claire Lhuillier, Lucillia Bezu, Fernando Aranda, Takahiro Yamazaki, Oliver Kepp, Jitka Fucikova, Radek Spisek, Sandra Demaria, Silvia C Formenti, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
Immune checkpoint blockers (ICBs) are literally revolutionizing the clinical management of an ever more diversified panel of oncological indications. Although considerable attention persists around the inhibition of cytotoxic T lymphocyte-associated protein 4 (CTLA4) and programmed cell death 1 (PDCD1, best known as PD-1) signaling, several other co-inhibitory T-cell receptors are being evaluated as potential targets for the development of novel ICBs. Moreover, substantial efforts are being devoted to the identification of biomarkers that reliably predict the likelihood of each patient to obtain clinical benefits from ICBs in the absence of severe toxicity...
2017: Oncoimmunology
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