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https://www.readbyqxmd.com/read/27893434/neuroinflammatory-and-cognitive-consequences-of-combined-radiation-and-immunotherapy-in-a-novel-preclinical-model
#1
Gwendolyn J McGinnis, David Friedman, Kristina H Young, Eileen Ruth S Torres, Charles R Thomas, Michael J Gough, Jacob Raber
BACKGROUND: Cancer patients often report behavioral and cognitive changes following cancer treatment. These effects can be seen in patients who have not yet received treatment or have received only peripheral (non-brain) irradiation. Novel treatments combining radiotherapy (RT) and immunotherapy (IT) demonstrate remarkable efficacy with respect to tumor outcomes by enhancing the proinflammatory environment in the tumor. However, a proinflammatory environment in the brain mediates cognitive impairments in other neurological disorders and may affect brain function in cancer patients receiving these novel treatments...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27873300/local-checkpoint-inhibition-of-ctla-4-as-a-monotherapy-or-in-combination-with-anti-pd1-prevents-the-growth-of-murine-bladder-cancer
#2
Luuk van Hooren, Linda C Sandin, Igor Moskalev, Peter Ellmark, Anna Dimberg, Peter Black, Thomas H Tötterman, Sara M Mangsbo
Checkpoint blockade of CTLA-4 results in long-lasting survival benefits in metastatic cancer patients. However, patients treated with CTLA-4 blockade have suffered from immune related adverse events, most likely due to the breadth of the induced T-cell activation. Here, we investigated the efficacy of a local low-dose anti-CTLA-4 administration for treatment of subcutaneous or orthotopic MB49 bladder carcinoma in C57BL/6 mice. When MB49 tumors were grown subcutaneously, peritumoral injection of anti-CTLA-4 treatment was equally effective as intravenous or subcutaneous (non-tumor bearing flank) administration...
November 22, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27864228/ifn%C3%AE-mutations-prompt-ctla-4-inhibitor-resistance
#3
(no author information available yet)
A recent study pinpoints loss of IFNγ signaling as one reason why many patients do not respond to the CTLA-4 inhibitor ipilimumab. Analyzing whole-exome tumor sequencing data from 16 patients with melanoma, the researchers found multiple copy-number alterations that led to the loss of key IFNγ pathway genes in 12 ipilimumab nonresponders. Mice bearing melanoma tumors that lacked one of these genes, IFNGR1, also had an impaired response to anti-CTLA-4 therapy and significantly reduced overall survival, compared with their counterparts whose tumors had intact IFNGR1...
November 18, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27846884/future-perspectives-in-melanoma-research-meeting-report-from-the-melanoma-bridge-napoli-december-1st-4th-2015
#4
Paolo A Ascierto, Sanjiv Agarwala, Gerardo Botti, Alessandra Cesano, Gennaro Ciliberto, Michael A Davies, Sandra Demaria, Reinhard Dummer, Alexander M Eggermont, Soldano Ferrone, Yang Xin Fu, Thomas F Gajewski, Claus Garbe, Veronica Huber, Samir Khleif, Michael Krauthammer, Roger S Lo, Giuseppe Masucci, Giuseppe Palmieri, Michael Postow, Igor Puzanov, Ann Silk, Stefani Spranger, David F Stroncek, Ahmad Tarhini, Janis M Taube, Alessandro Testori, Ena Wang, Jennifer A Wargo, Cassian Yee, Hassane Zarour, Laurence Zitvogel, Bernard A Fox, Nicola Mozzillo, Francesco M Marincola, Magdalena Thurin
The sixth "Melanoma Bridge Meeting" took place in Naples, Italy, December 1st-4th, 2015. The four sessions at this meeting were focused on: (1) molecular and immune advances; (2) combination therapies; (3) news in immunotherapy; and 4) tumor microenvironment and biomarkers. Recent advances in tumor biology and immunology has led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS) of cancer patients. Immunotherapies in particular have emerged as highly successful approaches to treat patients with cancer including melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's disease...
November 15, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27843208/immunotherapy-in-metastatic-prostate-cancer
#5
REVIEW
Susan F Slovin
INTRODUCTION: Prostate cancer remains a challenge as a target for immunological approaches. The approval of the first cell-based immune therapy, Sipuleucel-T for prostate cancer introduced prostate cancer as a solid tumor with the potential to be influenced by the immune system. METHODS: We reviewed articles on immunological management of prostate cancer and challenges that lie ahead for such strategies. RESULTS: Treatments have focused on the identification of novel cell surface antigens thought to be unique to prostate cancer...
October 2016: Indian Journal of Urology: IJU: Journal of the Urological Society of India
https://www.readbyqxmd.com/read/27832664/acute-interstitial-nephritis-related-to-immune-checkpoint-inhibitors
#6
Julie Belliere, Nicolas Meyer, Julien Mazieres, Sylvie Ollier, Serge Boulinguez, Audrey Delas, David Ribes, Stanislas Faguer
BACKGROUND: Immune checkpoint inhibitors (anti-PD1 or anti-CTLA-4) are increasingly used in various cancers. Immune checkpoint inhibitors (ICI)-related renal disorders are poorly described (9 cases) and were only related to Ipilimumab. METHODS: Retrospective collection of clinical charts of all the patients admitted for renal disorders following ICI in the University Hospital of Toulouse (France). RESULTS: We report on adverse renal events that occurred in three patients treated with anti-PD1 (nivolumab or pembrolizumab) or anti-CTLA-4 (ipilimumab)...
November 10, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27827885/is-there-still-room-for-cancer-vaccines-at-the-era-of-checkpoint-inhibitors
#7
REVIEW
Soumaya Karaki, Marie Anson, Thi Tran, Delphine Giusti, Charlotte Blanc, Stephane Oudard, Eric Tartour
Checkpoint inhibitor (CPI) blockade is considered to be a revolution in cancer therapy, although most patients (70%-80%) remain resistant to this therapy. It has been hypothesized that only tumors with high mutation rates generate a natural antitumor T cell response, which could be revigorated by this therapy. In patients with no pre-existing antitumor T cells, a vaccine-induced T cell response is a rational option to counteract clinical resistance. This hypothesis has been validated in preclinical models using various cancer vaccines combined with inhibitory pathway blockade (PD-1-PDL1-2, CTLA-4-CD80-CD86)...
November 3, 2016: Vaccines
https://www.readbyqxmd.com/read/27826115/prussian-blue-nanoparticle-based-photothermal-therapy-combined-with-checkpoint-inhibition-for-photothermal-immunotherapy-of-neuroblastoma
#8
Juliana Cano-Mejia, Rachel A Burga, Elizabeth E Sweeney, John P Fisher, Catherine M Bollard, Anthony D Sandler, Conrad Russell Y Cruz, Rohan Fernandes
We describe "photothermal immunotherapy," which combines Prussian blue nanoparticle (PBNP)-based photothermal therapy (PTT) with anti-CTLA-4 checkpoint inhibition for treating neuroblastoma, a common, hard-to-treat pediatric cancer. PBNPs exhibit pH-dependent stability, which makes them suitable for intratumorally-administered PTT. PBNP-based PTT is able to lower tumor burden and prime an immune response, specifically an increased infiltration of lymphocytes and T cells to the tumor area, which is complemented by the antitumor effects of anti-CTLA-4 immunotherapy, providing a more durable treatment against neuroblastoma in an animal model...
November 4, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/27797838/systemic-sarcoidosis-first-manifesting-in-a-tattoo-in-the-setting-of-immune-checkpoint-inhibition
#9
Charissa Kim, Jianjun Gao, Vickie R Shannon, Arlene Siefker-Radtke
The use of immune checkpoint inhibitors is revolutionising the treatment of cancer. However, their unique toxicity profile is substantially different from what has been observed with traditional chemotherapy, resulting in a novel learning curve for medical oncologists. Early recognition of these toxicities can make a substantial impact in ameliorating these side effects in the oncological and medical-surgical fields. Here, we present a case of Lofgren syndrome sarcoidosis, which first manifested in a tattoo in a patient with metastatic urothelial cancer on therapy with anti-CTLA-4 (ipilimumab) and anti-PD1 (nivolumab)...
October 26, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27782752/therapy-implications-of-the-role-of-interleukin-2-in-cancer
#10
Paolo Lissoni
Despite its apparent failure in cancer therapy, IL-2 still remains fundamental in the activation of antitumor immunity. Areas covered: The aim of this review is the reinterpretation of the role of IL-2 in anticancer immunity, according to knowledge gained of the cytokine network, by highlighting its importance in inducing T helper-1 (TH1) cell proliferation, natural killer (NK) actHivation and IL-12 secretion. However, its main negative effect is the stimulation of regulatory T cells (Tregs), which in contrast suppresses anticancer immunity...
October 26, 2016: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/27776519/novel-algorithmic-approach-predicts-tumor-mutation-load-and-correlates-with-immunotherapy-clinical-outcomes-using-a-defined-gene-mutation-set
#11
Jason Roszik, Lauren E Haydu, Kenneth R Hess, Junna Oba, Aron Y Joon, Alan E Siroy, Tatiana V Karpinets, Francesco C Stingo, Veera Baladandayuthapani, Michael T Tetzlaff, Jennifer A Wargo, Ken Chen, Marie-Andrée Forget, Cara L Haymaker, Jie Qing Chen, Funda Meric-Bernstam, Agda K Eterovic, Kenna R Shaw, Gordon B Mills, Jeffrey E Gershenwald, Laszlo G Radvanyi, Patrick Hwu, P Andrew Futreal, Don L Gibbons, Alexander J Lazar, Chantale Bernatchez, Michael A Davies, Scott E Woodman
BACKGROUND: While clinical outcomes following immunotherapy have shown an association with tumor mutation load using whole exome sequencing (WES), its clinical applicability is currently limited by cost and bioinformatics requirements. METHODS: We developed a method to accurately derive the predicted total mutation load (PTML) within individual tumors from a small set of genes that can be used in clinical next generation sequencing (NGS) panels. PTML was derived from the actual total mutation load (ATML) of 575 distinct melanoma and lung cancer samples and validated using independent melanoma (n = 312) and lung cancer (n = 217) cohorts...
October 25, 2016: BMC Medicine
https://www.readbyqxmd.com/read/27775332/how-reactive-metabolites-induce-an-immune-response-that-sometimes-leads-to-an-idiosyncratic-drug-reaction
#12
Tiffany Elizabeth Cho, Jack Uetrecht
Little is known with certainty about the mechanisms of idiosyncratic drug reactions (IDRs); however, there is substantive evidence that reactive metabolites are involved in most, but not all, IDRs. In addition, evidence also suggests that most IDRs are immune mediated. That raises the question of how reactive metabolites induce an immune response that can lead to an IDR. The dominant hypotheses are the hapten and danger hypotheses. These are complementary hypotheses: a reactive metabolite can act as a hapten to produce neoantigens, and it can also cause cell damage leading to the release of danger-associated molecular pattern molecules that activate antigen presenting cells...
October 24, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27774435/combining-radiation-therapy-with-immune-checkpoint-blockade-for-central-nervous-system-malignancies
#13
Neil M D'Souza, Penny Fang, Jennifer Logan, Jinzhong Yang, Wen Jiang, Jing Li
Malignancies of the central nervous system (CNS), particularly glioblastoma and brain metastases from a variety of disease sites, are difficult to treat despite advances in multimodality approaches consisting of surgery, chemotherapy, and radiation therapy (RT). Recent successes of immunotherapeutic strategies including immune checkpoint blockade (ICB) via anti-PD-1 and anti-CTLA-4 antibodies against aggressive cancers, such as melanoma, non-small cell lung cancer, and renal cell carcinoma, have presented an exciting opportunity to translate these strategies for CNS malignancies...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27770382/immune-checkpoint-inhibitors-for-cancer-treatment
#14
REVIEW
Junsik Park, Minsuk Kwon, Eui-Cheol Shin
During immune responses antigen-specific T cells are regulated by several mechanisms, including through inhibitory receptors and regulatory T cells, to avoid excessive or persistent immune responses. These regulatory mechanisms, which are called 'immune checkpoints', suppress T cell responses, particularly in patients with chronic viral infections and cancer where viral antigens or tumor antigens persist for a long time and contribute to T cell exhaustion. Among these regulatory mechanisms, cytotoxic T lymphocyte associated protein-4 (CTLA-4) and programmed cell death 1 (PD-1) are the most well-known receptors and both have been targeted for drug development...
November 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27769803/ubiquitin-specific-protease-7-inhibition-impairs-tip60-dependent-foxp3-t-regulatory-cell-function-and-promotes-antitumor-immunity
#15
Liqing Wang, Suresh Kumar, Satinder Dahiya, Feng Wang, Jian Wu, Kheng Newick, Rongxiang Han, Arabinda Samanta, Ulf H Beier, Tatiana Akimova, Tricia R Bhatti, Benjamin Nicholson, Mathew P Kodrasov, Saket Agarwal, David E Sterner, Wei Gu, Joseph Weinstock, Tauseef R Butt, Steven M Albelda, Wayne W Hancock
Foxp3+ T-regulatory (Treg) cells are known to suppress protective host immune responses to a wide variety of solid tumors, but their therapeutic targeting is largely restricted to their transient depletion or "secondary" modulation, e.g. using anti-CTLA-4 monoclonal antibody. Our ongoing studies of the post-translational modifications that regulate Foxp3 demonstrated that the histone/protein acetyltransferase, Tip60, plays a dominant role in promoting acetylation, dimerization and function in Treg cells. We now show that the ubiquitin-specific protease, Usp7, controls Treg function largely by stabilizing the expression and promoting the multimerization of Tip60 and Foxp3...
October 15, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27728898/relevance-of-serum-biomarkers-associated-with-melanoma-during-follow-up-of-anti-ctla-4-immunotherapy
#16
Joana Felix, Bruno Cassinat, Raphael Porcher, Marie-Hélène Schlageter, Eve Maubec, Cécile Pages, Barouyr Baroudjian, Laurence Homyrda, Wahid Boukouaci, Ryad Tamouza, Martine Bagot, Anne Caignard, Antoine Toubert, Céleste Lebbé, Hélène Moins-Teisserenc
Metastatic melanoma is a rapidly spreading cancer whose prognosis remains poor although important therapy advances in recent years. Ipilimumab, an anti-CTLA-4 immunotherapy used in advanced melanoma, is an effective immunotherapy alone or combined with other agents but with few predictive biomarkers of response. Here, we sought to analyze the potential of S100B, MIA, soluble MICA, anti-MICA antibodies and LDH as serum biomarkers of response and survival in a cohort of 77 advanced melanoma patients subjected to ipilimumab...
October 8, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27725678/immunotherapy-interferon-in-anti-ctla-4-responses
#17
David Killock
No abstract text is available yet for this article.
November 2016: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/27699271/tgf-%C3%AE-and-vegf-cooperatively-control-the-immunotolerant-tumor-environment-and-the-efficacy-of-cancer-immunotherapies
#18
Tristan Courau, Djamel Nehar-Belaid, Laura Florez, Béatrice Levacher, Thomas Vazquez, Faustine Brimaud, Bertrand Bellier, David Klatzmann
Tregs imprint an early immunotolerant tumor environment that prevents effective antitumor immune responses. Using transcriptomics of tumor tissues, we identified early upregulation of VEGF and TGF-β pathways compatible with tolerance imprinting. Silencing of VEGF or TGF-β in tumor cells induced early and pleiotropic modulation of immune-related transcriptome signatures in tumor tissues. These were surprisingly similar for both silenced tumors and related to common downstream effects on Tregs. Silencing of VEGF or TGF-β resulted in dramatically delayed tumor growth, associated with decreased Tregs and myeloid-derived suppressor cells and increased effector T cell activation in tumor infiltrates...
June 16, 2016: JCI Insight
https://www.readbyqxmd.com/read/27697858/il-2-variant-circumvents-icos-regulatory-t-cell-expansion-and-promotes-nk-cell-activation
#19
Geok Choo Sim, Chengwen Liu, Ena Wang, Hui Liu, Caitlin Creasy, Zhimin Dai, Willem W Overwijk, Jason Roszik, Francesco M Marincola, Patrick Hwu, Elizabeth A Grimm, Laszlo G Radvanyi
Clinical responses to high-dose IL-2 therapy are limited due to selective expansion of CD4+CD25+oxp3+ T-regulatory cells (Tregs) especially ICOS+Tregs, rather than NK cells and effector T cells. These ICOS+Tregs are highly suppressive and constitutively express high levels of IL-2Ralpha (CD25) and CD39. Here, we characterized the effect of a mutant form of IL-2 (F42K), which preferentially binds to the lower affinity IL-2Rbetagamma with reduced binding to CD25, on Tregs, effector NK cells, and T-cell subsets...
October 3, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27675964/outcomes-of-melanoma-brain-metastases-treated-with-stereotactic-radiosurgery-and-anti-pd-1-therapy-anti-ctla-4-therapy-braf-inhibitor-or-conventional-chemotherapy
#20
K A Ahmed, Y A Abuodeh, C Hogue, D G Stallworth, A O Naghavi, S Kim, S Sarangkasiri, P A S Johnstone, H M Yu, N I Khushalani, A B Etame, L B Harrison, J J Caudell
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
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