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glioblastoma immunotherapy

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https://www.readbyqxmd.com/read/28178682/comprehensive-analysis-of-pd-l1-expression-in-glioblastoma-multiforme
#1
Dieter Henrik Heiland, Gerrit Haaker, Daniel Delev, Bianca Mercas, Waseem Masalha, Sabrina Heynckes, Annette Gäbelein, Dietmar Pfeifer, Maria Stella Carro, Astrid Weyerbrock, Marco Prinz, Oliver Schnell
Glioblastoma multiforme are highly malignant brain tumours with frequent genetic and epigenetic alterations. The poor clinical outcome of these tumours necessitates the development of new treatment options. Immunotherapies for glioblastoma multiforme including PD1/PD-L1 inhibition are currently tested in ongoing clinical trials. The purpose of this study was to investigate the molecular background of PD-L1 expression in glioblastoma multiforme and to find associated pathway activation and genetic alterations...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28142059/intracerebral-injection-of-cpg-oligonucleotide-for-patients-with-de-novo-glioblastoma-a-phase-ii-multicentric-randomised-study
#2
Renata Ursu, Alexandre Carpentier, Philippe Metellus, Vincent Lubrano, Florence Laigle-Donadey, Laurent Capelle, Jacques Guyotat, Olivier Langlois, Luc Bauchet, Kristell Desseaux, Annick Tibi, Olivier Chinot, Jérôme Lambert, Antoine F Carpentier
BACKGROUND: Immunostimulating oligodeoxynucleotides containing unmethylated cytosine-guanosine motifs (CpG-ODN) have shown a promising efficacy in several cancer models when injected locally. A previous phase II study of CpG-ODN in patients with recurrent glioblastoma (GBM) has suggested some activity and has shown a limited toxicity. This multicentre single-blinded randomised phase II trial was designed to study the efficacy of a local treatment by CpG-ODN in patients with de novo glioblastomas...
January 28, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28138787/the-development-of-dendritic-cell-vaccine-based-immunotherapies-for-glioblastoma
#3
REVIEW
David A Reardon, Duane A Mitchell
In this review, we focus on the biologic advantages of dendritic cell-based vaccinations as a therapeutic strategy for cancer as well as preclinical and emerging clinical data associated with such approaches for glioblastoma patients.
January 30, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28116121/syndecan-4-as-a-biomarker-to-predict-clinical-outcome-for-glioblastoma-multiforme-treated-with-wt1-peptide-vaccine
#4
Satoshi Takashima, Yoshihiro Oka, Fumihiro Fujiki, Soyoko Morimoto, Hiroko Nakajima, Yoshiki Nakae, Jun Nakata, Sumiyuki Nishida, Naoki Hosen, Naoya Tatsumi, Kenji Mizuguchi, Naoya Hashimoto, Yusuke Oji, Akihiro Tsuboi, Atsushi Kumanogoh, Haruo Sugiyama
AIM: In cancer immunotherapy, biomarkers are important for identification of responsive patients. This study was aimed to find biomarkers that predict clinical outcome of WT1 peptide vaccination. MATERIALS & METHODS: Candidate genes that were expressed differentially between long- and short-term survivors were identified by cDNA microarray analysis of peripheral blood mononuclear cells that were extracted from 30 glioblastoma patients (discovery set) prior to vaccination and validated by quantitative RT-PCR using discovery set and different 23 patients (validation set)...
December 2016: Future Science OA
https://www.readbyqxmd.com/read/28111040/-immunotherapy-in-brain-tumors
#5
Emilie De Carli, Matthieu Delion, Audrey Rousseau
Diffuse gliomas represent the most common primary central nervous system (CNS) tumors in adults and children alike. Glioblastoma is the most frequent and malignant form of diffuse glioma with a median overall survival of 15 months despite aggressive treatments. New therapeutic approaches are needed to prolong survival in this always fatal disease. The CNS has been considered for a long time as an immune privileged organ, in part because of the existence of the blood-brain barrier. Nonetheless, immunotherapy is a novel approach in the therapeutic management of glioma patients, which has shown promising results in several clinical trials, especially in the adult population...
January 19, 2017: Annales de Pathologie
https://www.readbyqxmd.com/read/28109751/cord-blood-natural-killer-cells-expressing-a-dominant-negative-tgf-%C3%AE-receptor-implications-for-adoptive-immunotherapy-for-glioblastoma
#6
Eric S Yvon, Rachel Burga, Allison Powell, Conrad R Cruz, Rohan Fernandes, Cecilia Barese, Tuongvan Nguyen, Mohamed S Abdel-Baki, Catherine M Bollard
Cord blood (CB) natural killer (NK) cells are promising effector cells for tumor immunotherapy but are currently limited by immune-suppressive cytokines in the tumor microenvironment, such as transforming growth factor (TGF-β). We observed that TGF-β inhibits expression of activating receptors such as NKG2D and DNAM1 and decreases killing activity against glioblastoma tumor cells through inhibition of perforin secretion. To overcome the detrimental effects of TGF-β, we engrafted a dominant negative TGF-β receptor II (DNRII) on CB-derived NK cells by retroviral transduction and evaluated their ability to kill glioblastoma cells in the presence of TGF-β...
January 19, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28094259/immunotherapy-glioblastoma-regression-obtained-with-car-t-cells
#7
Peter Sidaway
No abstract text is available yet for this article.
January 17, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28076333/surgical-debulking-promotes-recruitment-of-macrophages-and-triggers-glioblastoma-phagocytosis-in-combination-with-cd47-blocking-immunotherapy
#8
Huaiyang Zhu, Lina Leiss, Ning Yang, Cecilie B Rygh, Siddhartha S Mitra, Samuel H Cheshier, Irving L Weissman, Bin Huang, Hrvoje Miletic, Rolf Bjerkvig, Per Ø Enger, Xingang Li, Jian Wang
Surgical resection is a standard component of treatment in the clinical management of patients with glioblastoma multiforme (GBM). However, experimental therapies are rarely investigated in the context of tumor debulking in preclinical models. Here, a surgical debulking GBM xenograft model was developed in nude rats, and was used in combination with CD47 blocking immunotherapy, a novel treatment strategy that triggers phagocytosis of tumor cells by macrophages in diverse cancer types including GBM. Orthotopic patient-derived xenograft tumors expressing CD47 were resected at 4 weeks after implantation and immediately thereafter treated with anti-CD47 or control antibodies injected into the cavity...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28070598/advanced-mri-assessment-to-predict-benefit-of-anti-programmed-cell-death-1-protein-immunotherapy-response-in-patients-with-recurrent-glioblastoma
#9
Lei Qin, Xiang Li, Amanda Stroiney, Jinrong Qu, Jeffrey Helgager, David A Reardon, Geoffrey S Young
INTRODUCTION: We describe the imaging findings encountered in GBM patients receiving immune checkpoint blockade and assess the potential of quantitative MRI biomarkers to differentiate patients who derive therapeutic benefit from those who do not. METHODS: A retrospective analysis was performed on longitudinal MRIs obtained on recurrent GBM patients enrolled on clinical trials. Among 10 patients with analyzable data, bidirectional diameters were measured on contrast enhanced T1 (pGd-T1WI) and volumes of interest (VOI) representing measurable abnormality suggestive of tumor were selected on pGdT1WI (pGdT1 VOI), FLAIR-T2WI (FLAIR VOI), and ADC maps...
January 9, 2017: Neuroradiology
https://www.readbyqxmd.com/read/28056258/-advance-of-molecular-subtyping-and-precise-treatment-for-gliomas
#10
W Hua, Y Mao
With the advance of genomics research, there have been a new breakthrough in the molecular classification of gliomas. Glioblastoma (WHO grade Ⅳ) could be subtyped to proneural, neural, classical, and mesochymal according to the mRNA expression. Lower grade gliomas (WHO grade Ⅱ and Ⅲ) could be divided into 5 types using 1p/19q co-deletion, isocitrate dehydrogenase(IDH) mutation, and TERTp (promotor region) mutation. In 2016, a new classification of tumors of the central nervous system was proposed, and some new markers such as IDH1 mutation were introduced into the diagnosis of gliomas...
1, 2017: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
https://www.readbyqxmd.com/read/28017775/the-network-of-immunosuppressive-pathways-in-glioblastoma
#11
REVIEW
Davide Mangani, Michael Weller, Patrick Roth
Glioblastoma remains a fatal tumor despite increased knowledge regarding the complex signalling pathways that drive this devastating disease. Recently, immunotherapeutic approaches have shown remarkable and durable responses in various cancers including metastatic melanoma and advanced non-small cell lung cancer. So far, it remains unclear whether these immunotherapeutics may also work against glioblastoma and other tumors residing in the central nervous system. It is well known that patients with glioblastoma suffer from profound local immunosuppression that represents the major hurdle to overcome in the context of immunotherapy...
December 22, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28011470/advances-in-experimental-targeted-therapy-and-immunotherapy-for-patients-with-glioblastoma-multiforme
#12
REVIEW
Jiri Polivka, Jiri Polivka, Lubos Holubec, Tereza Kubikova, Vladimir Priban, Ondrej Hes, Kristyna Pivovarcikova, Inka Treskova
Glioblastoma multiforme (GBM) represents the most malignant primary brain tumor in adults with generally dismal prognosis, early clinical deterioration and high mortality. GBM is extremely invasive, characterized by intense and aberrant vascularization and high resistance to multimodal treatment. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) has very limited effectiveness, with median overall survival of patients no longer than 15 months. Progress in genetics and epigenetics of GBM over the past decade has revealed various aberrations in cellular signaling pathways, the tumor microenvironment, and pathological angiogenesis...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28003545/anti-pd-1-antitumor-immunity-is-enhanced-by-local-and-abrogated-by-systemic-chemotherapy-in-gbm
#13
Dimitrios Mathios, Jennifer E Kim, Antonella Mangraviti, Jillian Phallen, Chul-Kee Park, Christopher M Jackson, Tomas Garzon-Muvdi, Eileen Kim, Debebe Theodros, Magdalena Polanczyk, Allison M Martin, Ian Suk, Xiaobu Ye, Betty Tyler, Chetan Bettegowda, Henry Brem, Drew M Pardoll, Michael Lim
The immunosuppressive effects of chemotherapy present a challenge for designing effective cancer immunotherapy strategies. We hypothesized that although systemic chemotherapy (SC) exhibits negative immunologic effects, local chemotherapy (LC) can potentiate an antitumor immune response. We show that LC combined with anti-programmed cell death protein 1 (PD-1) facilitates an antitumor immune response and improves survival (P < 0.001) in glioblastoma. LC-treated mice had increased infiltration of tumor-associated dendritic cells and clonal expansion of antigen-specific T effector cells...
December 21, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/28000534/adoptive-immunotherapy-for-the-treatment-of-glioblastoma-progress-and-possibilities
#14
Shunichiro Kuramitsu, Akane Yamamichi, Fumiharu Ohka, Kazuya Motomura, Masahito Hara, Atsushi Natsume
Patients with glioblastoma have a very poor prognosis. Adoptive cellular therapy (ACT) is defined as the collection of circulating or tumor-infiltrating lymphocytes, their selection, modification, expansion and activation, and their re-administration to patients in order to induce antitumor activity. Although various ACTs have been attempted, most failed to improve the outcome. Immune checkpoint blockade antibodies and T cell engineering with tumor-specific chimeric antigen receptors suggest the emergence of a new era of immunotherapy...
December 2016: Immunotherapy
https://www.readbyqxmd.com/read/27993092/novel-vaccines-for-glioblastoma-clinical-update-and-perspective
#15
Evan K Winograd, Michael J Ciesielski, Robert A Fenstermaker
Glioblastoma is the most common primary brain cancer. Aggressive treatment with surgery, radiation therapy and chemotherapy provides limited overall survival benefit. Glioblastomas have a formidable tumor microenvironment that is hostile to immunological effector cells and these cancers produce profound systemic immunosuppression. However, surgical resection of these tumors creates conditions that favor the use of immunotherapeutic strategies. Therefore, extensive surgical resection, when feasible, will remain part of the equation to provide an environment in which active specific immunotherapy has the greatest chance of working...
November 2016: Immunotherapy
https://www.readbyqxmd.com/read/27989218/the-safety-of-available-immunotherapy-for-the-treatment-of-glioblastoma
#16
S Harrison Farber, Aladine A Elsamadicy, Ahmet Fatih Atik, Carter M Suryadevara, Pakawat Chongsathidkiet, Peter E Fecci, John H Sampson
Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Current standard of care involves maximal surgical resection combined with adjuvant chemoradiation. Growing support exists for a role of immunotherapy in treating these tumors with the goal of targeted cytotoxicity. Here we review data on the safety for current immunotherapies being tested in GBM. Areas covered: Safety data from published clinical trials, including ongoing clinical trials were reviewed. Immunotherapeutic classes currently under investigation in GBM include various vaccination strategies, adoptive T cell immunotherapy, immune checkpoint blockade, monoclonal antibodies, and cytokine therapies...
January 3, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27989100/pd-l1-expression-and-combined-status-of-pd-l1-pd-1-positive-tumor-infiltrating-mononuclear-cell-density-predict-prognosis-in-glioblastoma-patients
#17
Jiheun Han, Yongkil Hong, Youn Soo Lee
BACKGROUND: Programmed death ligand 1 (PD-L1) in tumor cells is known to promote immune escape of cancer by interacting with programmed cell death 1 (PD-1) in tumor infiltrating immune cells. Immunotherapy targeting these molecules is emerging as a new strategy for the treatment of glioblastoma (GBM). Understanding the relationship between the PD-L1/PD-1 axis and prognosis in GBM patients may be helpful to predict the effects of immunotherapy. METHODS: PD-L1 expression and PD-1-positive tumor infiltrating mononuclear cell (PD-1+tumor infiltrating mononuclear cell [TIMC]) density were evaluated using tissue microarray containing 54 GBM cases by immunohistochemical analysis; the associations with patient clinical outcomes were evaluated...
January 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/27974697/surrogate-in-vitro-activation-of-innate-immunity-synergizes-with-interleukin-7-to-unleash-rapid-antigen-driven-outgrowth-of-cd4-and-cd8-human-peripheral-blood-t-cells-naturally-recognizing-muc1-her2-neu-and-other-tumor-associated-antigens
#18
Latha B Pathangey, Dustin B McCurry, Sandra J Gendler, Ana L Dominguez, Jessica E Gorman, Girish Pathangey, Laurie A Mihalik, Yushe Dang, Mary L Disis, Peter A Cohen
Effective adoptive immunotherapy has proved elusive for many types of human cancer, often due to difficulties achieving robust expansion of natural tumor-specific T-cells from peripheral blood. We hypothesized that antigen-driven T-cell expansion might best be triggered in vitro by acute activation of innate immunity to mimic a life-threatening infection. Unfractionated peripheral blood mononuclear cells (PBMC) were subjected to a two-step culture, first synchronizing their exposure to exogenous antigens with aggressive surrogate activation of innate immunity, followed by γ-chain cytokine-modulated T-cell hyperexpansion...
December 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27942839/immune-modulation-associated-with-vascular-endothelial-growth-factor-vegf-blockade-in-patients-with-glioblastoma
#19
Alissa A Thomas, Jan L Fisher, Thomas H Hampton, Brock C Christensen, Gregory J Tsongalis, Gilbert J Rahme, Chery A Whipple, Sandra E Steel, Melissa C Davis, Arti B Gaur, Lionel D Lewis, Marc S Ernstoff, Camilo E Fadul
BACKGROUND: Vascular endothelial growth factor (VEGF), in addition to being pro-angiogenic, is an immunomodulatory cytokine systemically and in the tumor microenvironment. We previously reported the immunomodulatory effects of radiation and temozolomide (TMZ) in newly diagnosed glioblastoma. This study aimed to assess changes in peripheral blood mononuclear cell (PBMC) populations, plasma cytokines, and growth factor concentrations following treatment with radiation, TMZ, and bevacizumab (BEV)...
December 9, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27895032/molecular-pathways-receptor-ectodomain-shedding-in-treatment-resistance-and-monitoring-of-cancer
#20
Miles A Miller, Ryan J Sullivan, Douglas A Lauffenburger
Proteases known as sheddases cleave the extracellular domains of their substrates from the cell surface. The A Disintegrin and Metalloproteinases ADAM10 and ADAM17 are among the most prominent sheddases, being widely expressed in many tissues, frequently overexpressed in cancer, and promiscuously cleaving diverse substrates. It is increasingly clear that the proteolytic shedding of transmembrane receptors impacts pathophysiology and drug response. Receptor substrates of sheddases include the cytokine receptors TNFR1 and IL6R; the Notch receptors; type-I and -III TGFβ receptors; receptor tyrosine kinases (RTK) such as HER2, HER4, and VEGFR2; and, in particular, MET and TAM-family RTKs AXL and Mer (MerTK)...
February 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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