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glioblastoma immunotherapy

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https://www.readbyqxmd.com/read/28919997/increased-infiltration-and-tolerised-antigen-specific-cd8-tem-cells-in-tumor-but-not-peripheral-blood-have-no-impact-on-survival-of-hcmv-glioblastoma-patients
#1
M Bahador, A Gras Navarro, M A Rahman, M Dominguez-Valentin, S Sarowar, E Ulvestad, G Njølstad, S A Lie, E K Kristoffersen, E Bratland, M Chekenya
Human cytomegalovirus (HCMV) antigens in glioblastoma (GBM) present opportunities for personalised immunotherapy. However, their presence in GBM tissue is still under debate, and evidence of their impact on functional immune responses and prognosis is sparse. Here, we investigated the presence of pp65 (UL83) and immediate early 1 (IE-1) HCMV antigens in a cohort of Norwegian GBM patients (n = 177), using qPCR, immunohistochemistry, and serology. HCMV status was then used to investigate whether viral antigens influenced immune cell phenotype, infiltration, activation and patient survival...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919992/molecular-and-clinical-characterization-of-tim-3-in-glioma-through-1-024-samples
#2
Guanzhang Li, Zheng Wang, Chuanbao Zhang, Xing Liu, Jinquan Cai, Zhiliang Wang, Huimin Hu, Fan Wu, Zhaoshi Bao, Yanwei Liu, Liang Zhao, Tingyu Liang, Fan Yang, Ruoyu Huang, Wei Zhang, Tao Jiang
Background: Researches on immunotherapy of glioma has been increasing exponentially in recent years. However, autoimmune-like side effects of current immune checkpoint blockade hindered the clinical application of immunotherapy in glioma. The discovery of the TIM-3, a tumor-specific immune checkpoint, has shed a new light on solution of this dilemma. We aimed at investigating the role of TIM-3 at transcriptome level and its relationship with clinical practice in glioma. Methods: A cohort of 325 glioma patients with RNA-seq data from Chinese Glioma Genome Atlas (CGGA project) was analyzed, and the results were well validated in TCGA RNA-seq data of 699 gliomas...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28912153/comprehensive-genomic-profiling-of-282-pediatric-low-and-high-grade-gliomas-reveals-genomic-drivers-tumor-mutational-burden-and-hypermutation-signatures
#3
Adrienne Johnson, Eric Severson, Laurie Gay, Jo-Anne Vergilio, Julia Elvin, James Suh, Sugganth Daniel, Mandy Covert, Garrett M Frampton, Sigmund Hsu, Glenn J Lesser, Kimberly Stogner-Underwood, Ryan T Mott, Sarah Z Rush, Jennifer J Stanke, Sonika Dahiya, James Sun, Prasanth Reddy, Zachary R Chalmers, Rachel Erlich, Yakov Chudnovsky, David Fabrizio, Alexa B Schrock, Siraj Ali, Vincent Miller, Philip J Stephens, Jeffrey Ross, John R Crawford, Shakti H Ramkissoon
BACKGROUND: Pediatric brain tumors are the leading cause of death for children with cancer in the U.S. Incorporating next-generation sequencing data for both pediatric low-grade (pLGGs) and high-grade gliomas (pHGGs) can inform diagnostic, prognostic, and therapeutic decision-making. MATERIALS AND METHODS: We performed comprehensive genomic profiling on 282 pediatric gliomas (157 pHGGs, 125 pLGGs), sequencing 315 cancer-related genes and calculating the tumor mutational burden (TMB; mutations per megabase [Mb])...
September 14, 2017: Oncologist
https://www.readbyqxmd.com/read/28912136/tumor-resection-boosts-therapeutic-efficacy-of-encapsulated-stem-cells-expressing-a-highly-secretable-variant-of-interferon-%C3%AE-in-glioblastomas
#4
Sung Hugh Choi, Daniel W Stuckey, Sara Pignatta, Clemens Reinshagen, Jasneet K Khalsa, Nicolaas C Roozendaal, Jordi Martinez-Quintanilla, Kaoru Tamura, Erhan Keles, Khalid Shah
PURPOSE: Despite tumor resection being the frontline clinical care for glioblastoma (GBM) patients, nearly all preclinical immune therapy models intends to treat established GBM tumor. Characterizing cytoreductive surgery-induced immune-response combined with the administration of immune cytokines has the potential of offering a new treatment paradigm of immune therapy for GBMs.  Experimental design: We developed syngeneic orthotopic mouse GBM models of tumor-resection and characterized the immune response of intact and resected tumors...
September 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28906259/radiation-and-immunotherapy-in-high-grade-gliomas-where-do-we-stand
#5
Elizabeth Reznik, Andrew W Smith, Shoshana Taube, Justin Mann, Menachem Z Yondorf, Bhupesh Parashar, A Gabriella Wernicke
High-grade glioma is the most common primary brain tumor, with glioblastoma multiforme (GBM) accounting for 52% of all brain tumors. The current standard of care (SOC) of GBM involves surgery followed by adjuvant fractionated radiotherapy and chemotherapy. However, little progress has been made in extending overall survival, progression-free survival, and quality of life. Attempts to characterize and customize treatment of GBM have led to mitigating the deleterious effects of radiotherapy using hypofractionated radiotherapy, as well as various immunotherapies as a promising strategy for the incurable disease...
September 12, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28895855/hematopoietic-stem-cell-approaches-to-cancer
#6
REVIEW
Jennifer E Adair, Sara P Kubek, Hans-Peter Kiem
Hematopoietic stem cells (HSCs) are unique in their ability to self-renew and generate all blood lineages for the entire life. HSC modification affects red blood cells, platelets, lymphocytes, and myeloid cells. Chemotherapy can result in myelosuppression, limiting effective chemotherapy administration. For diseases like glioblastoma, high expression of methlylguanine methyltransferase can inactivate alkylating agent chemotherapy. Here we discuss how HSCs can be modified to overcome this resistance, permitting sensitization of tumors to chemotherapy while simultaneously protecting the hematopoietic system...
October 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/28874539/detection-of-immune-responses-after-immunotherapy-in-glioblastoma-using-pet-and-mri
#7
Joseph P Antonios, Horacio Soto, Richard G Everson, Diana L Moughon, Anthony C Wang, Joey Orpilla, Caius Radu, Benjamin M Ellingson, Jason T Lee, Timothy Cloughesy, Michael E Phelps, Johannes Czernin, Linda M Liau, Robert M Prins
Contrast-enhanced MRI is typically used to follow treatment response and progression in patients with glioblastoma (GBM). However, differentiating tumor progression from pseudoprogression remains a clinical dilemma largely unmitigated by current advances in imaging techniques. Noninvasive imaging techniques capable of distinguishing these two conditions could play an important role in the clinical management of patients with GBM and other brain malignancies. We hypothesized that PET probes for deoxycytidine kinase (dCK) could be used to differentiate immune inflammatory responses from other sources of contrast-enhancement on MRI...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28873996/phase-i-ii-trial-of-combination-of-temozolomide-chemotherapy-and-immunotherapy-with-fusions-of-dendritic-and-glioma-cells-in-patients-with-glioblastoma
#8
Wi Jin Kim, W Christopher Newman, Nduka M Amankulor
No abstract text is available yet for this article.
July 1, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28864225/rna-interference-for-glioblastoma-therapy-innovation-ladder-from-the-bench-to-clinical-trials
#9
REVIEW
Eunice L Lozada-Delgado, Nilmary Grafals-Ruiz, Pablo E Vivas-Mejía
Glioblastoma multiforme (GBM) is the most common and deadliest type of primary brain tumor with a prognosis of 14months after diagnosis. Current treatment for GBM patients includes "total" tumor resection, temozolomide-based chemotherapy, radiotherapy or a combination of these options. Although, several targeted therapies, gene therapy, and immunotherapy are currently in the clinic and/or in clinical trials, the overall survival of GBM patients has hardly improved over the last two decades. Therefore, novel multitarget modalities are urgently needed...
August 29, 2017: Life Sciences
https://www.readbyqxmd.com/read/28863449/glioblastoma-targeted-therapy-updated-approaches-from-recent-biological-insights
#10
M Touat, A Idbaih, M Sanson, K L Ligon
Glioblastoma (WHO grade IV astrocytoma) is the most frequent primary brain tumor in adults, representing a highly heterogeneous group of neoplasms that are among the most aggressive and challenging cancers to treat. An improved understanding of the molecular pathways that drive malignancy in glioblastoma has led to the development of various biomarkers and the evaluation of several agents specifically targeting tumor cells and the tumor microenvironment. A number of rational approaches are being investigated, including therapies targeting tumor growth factor receptors and downstream pathways, cell cycle and epigenetic regulation, angiogenesis and antitumor immune response...
July 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28844499/rindopepimut-with-temozolomide-for-patients-with-newly-diagnosed-egfrviii-expressing-glioblastoma-act-iv-a-randomised-double-blind-international-phase-3-trial
#11
Michael Weller, Nicholas Butowski, David D Tran, Lawrence D Recht, Michael Lim, Hal Hirte, Lynn Ashby, Laszlo Mechtler, Samuel A Goldlust, Fabio Iwamoto, Jan Drappatz, Donald M O'Rourke, Mark Wong, Mark G Hamilton, Gaetano Finocchiaro, James Perry, Wolfgang Wick, Jennifer Green, Yi He, Christopher D Turner, Michael J Yellin, Tibor Keler, Thomas A Davis, Roger Stupp, John H Sampson
BACKGROUND: Rindopepimut (also known as CDX-110), a vaccine targeting the EGFR deletion mutation EGFRvIII, consists of an EGFRvIII-specific peptide conjugated to keyhole limpet haemocyanin. In the ACT IV study, we aimed to assess whether or not the addition of rindopepimut to standard chemotherapy is able to improve survival in patients with EGFRvIII-positive glioblastoma. METHODS: In this randomised, double-blind, phase 3 trial, we recruited patients aged 18 years and older with glioblastoma from 165 hospitals in 22 countries...
August 22, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28841803/tumor-treating-fields-a-novel-and-effective-therapy-for-glioblastoma-mechanism-efficacy-safety-and-future-perspectives
#12
Ping Zhu, Jay-Jiguang Zhu
BACKGROUND: Tumor treating fields (TTF, Optune®), one of the low-intensity alternating electric fields, have been demonstrated to disrupt mitosis and inhibit tumor growth with antimitotic properties in a variety of tumor types. The Food and Drug Administration (FDA) of the United States approved TTF for recurrent GBM and newly diagnosed GBM in 2011 and 2015, respectively. METHODS: A systematic review was conducted regarding the relevant studies published between January 1, 2000, and May 31, 2017 in PubMed database...
August 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28830878/constitutive-signaling-from-an-engineered-il-7-receptor-promotes-durable-tumor-elimination-by-tumor-redirected-t-cells
#13
Thomas Shum, Bilal Omer, Haruko Tashiro, Robert L Kruse, Dimitrios L Wagner, Kathan Parikh, Zhongzhen Yi, Tim Sauer, Daofeng Liu, Robin Parihar, Paul Castillo, Hao Liu, Malcolm K Brenner, Leonid S Metelitsa, Stephen Gottschalk, Cliona M Rooney
Successful adoptive T-cell immunotherapy of solid tumors will require improved expansion and cytotoxicity of tumor-directed T cells within tumors. Providing recombinant or transgenic cytokines may produce the desired benefits but are associated with significant toxicities, constraining clinical use. To circumvent this limitation, we constructed a constitutively signaling cytokine receptor, C7R, which potently triggers the IL-7 signaling axis but is unresponsive to extracellular cytokine. This strategy augments modified T-cell function following antigen exposure, but avoids stimulating bystander lymphocytes...
August 22, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28829151/validation-of-an-immunohistochemistry-assay-for-detection-of-cd155-the-poliovirus-receptor-in-malignant-gliomas
#14
Vidyalakshmi Chandramohan, Jeffrey D Bryant, Hailan Piao, Stephen T Keir, Eric S Lipp, Michaela Lefaivre, Kathryn Perkinson, Darell D Bigner, Matthias Gromeier, Roger E McLendon
CONTEXT: - The oncolytic polio-rhinovirus recombinant (PVSRIPO) has demonstrated promise in currently ongoing phase I/II clinical trials against recurrent glioblastoma and was granted breakthrough therapy designation by the Food and Drug Administration/Center for Biologics Evaluation and Research. A reliable clinical assay to document expression of the poliovirus receptor, CD155, in routinely available patient tumor samples is needed for continued clinical development of PVSRIPO oncolytic immunotherapy in primary brain tumors and beyond...
August 22, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28810141/a-viro-immunotherapy-triple-play-for-the-treatment-of-glioblastoma
#15
John C Bell, Carolina S Ilkow
In this issue of Cancer Cell, Saha et al. systematically test and optimize combination therapy strategies in a challenging model of glioblastoma. Durable complete responses were seen only when an oncolytic virus expressing IL12 was coupled with anti-CTLA-4 and anti-PD-1 therapeutics.
August 14, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28799547/immunotherapy-car-t-cells-in-glioblastoma
#16
Crunkhorn Sarah
No abstract text is available yet for this article.
September 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28790487/developing-therapies-for-brain-tumors-the-impact-of-the-johns-hopkins-hunterian-neurosurgical-research-laboratory
#17
Henry Brem, Eric W Sankey, Ann Liu, Antonella Mangraviti, Betty M Tyler
The Johns Hopkins Hunterian Neurosurgical Laboratory at the Johns Hopkins University School of Medicine was created in 1904 by Harvey Cushing and William Halsted and has had a long history of fostering surgical training, encouraging basis science research, and facilitating translational application. Over the past 30 years, the laboratory has addressed the paucity of brain tumor therapies. Pre-clinical work from the laboratory led to the development of carmustine wafers with initial US Food and Drug Administration (FDA) approval in 1996...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28763794/targeting-latency-associated-peptide-promotes-antitumor-immunity
#18
Galina Gabriely, Andre P da Cunha, Rafael M Rezende, Brendan Kenyon, Asaf Madi, Tyler Vandeventer, Nathaniel Skillin, Stephen Rubino, Lucien Garo, Maria A Mazzola, Panagiota Kolypetri, Amanda J Lanser, Thais Moreira, Ana Maria C Faria, Hans Lassmann, Vijay Kuchroo, Gopal Murugaiyan, Howard L Weiner
Regulatory T cells (Tregs) promote cancer by suppressing antitumor immune responses. We found that anti-LAP antibody, which targets the latency-associated peptide (LAP)/transforming growth factor-β (TGF-β) complex on Tregs and other cells, enhances antitumor immune responses and reduces tumor growth in models of melanoma, colorectal carcinoma, and glioblastoma. Anti-LAP decreases LAP(+) Tregs, tolerogenic dendritic cells, and TGF-β secretion and is associated with CD8(+) T cell activation. Anti-LAP increases infiltration of tumors by cytotoxic CD8(+) T cells and reduces CD103(+) CD8 T cells in draining lymph nodes and the spleen...
May 19, 2017: Science Immunology
https://www.readbyqxmd.com/read/28755993/breaching-barriers-in-glioblastoma-part-i-molecular-pathways-and-novel-treatment-approaches
#19
REVIEW
Ana Miranda, María Blanco-Prieto, João Sousa, Alberto Pais, Carla Vitorino
Glioblastoma multiforme (GBM) is the most common primary brain tumour, and the most aggressive in nature. The prognosis for patients with GBM remains poor, with a median survival time of only 1-2 years. The treatment failure relies on the development of resistance by tumour cells and the difficulty of ensuring that drugs effectively cross the dual blood brain barrier/blood brain tumour barrier. The advanced molecular and genetic knowledge has allowed to identify the mechanisms responsible for temozolomide resistance, which represents the standard of care in GBM, along with surgical resection and radiotherapy...
July 27, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28736431/combined-blockade-of-t-cell-immunoglobulin-and-mucin-domain-3-and-carcinoembryonic-antigen-related-cell-adhesion-molecule-1-results-in-durable-therapeutic-efficacy-in-mice-with-intracranial-gliomas
#20
Jinhu Li, Xiaodong Liu, Yijun Duan, Yueting Liu, Hongqin Wang, Shizhong Lian, Guotao Zhuang, Yimin Fan
BACKGROUND Glioblastoma multiforme (GBM) evades immune surveillance by inducing immunosuppression via receptor-ligand interactions between immune checkpoint molecules. T cell immunoglobulin and mucin domain 3 (Tim-3) is a key checkpoint receptor responsible for exhaustion and dysfunction of T cells and plays a critical role in immunosuppression. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been recently identified as a heterophilic ligand for Tim-3. MATERIAL AND METHODS We established an intracranial GBM model using C57BL/6 mice and GL261 cells, and treated the mice with single or combined monoclonal antibodies (mAbs) against Tim-3/CEACAM1...
July 24, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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