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glioblastoma immunotherapy

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https://www.readbyqxmd.com/read/29328445/the-effects-of-interleukin-2-and-rad-p53-as-a-treatment-for-glioblastoma
#1
Hai-Bo Qiao, Jia Li, Lian-Jie Lv, Ben-Jin Nie, Peng Lu, Feng Xue, Zhi-Ming Zhang
Interleukin 2 (IL-2) is an anti-cancer cytokine that stimulates T cell propagation, triggering innate and adaptive immunity. IL-2 has been used for cancer therapy and has achieved curative effects. Recombinant adenovirus p53 injection (rAd‑p53) is a gene therapeutic agent that may improve the prognosis of patients with glioblastoma (GBM). In the present study, the effect of combined IL‑2 and rAd‑p53 treatment was studied. The ability of IL‑2 to stimulate immunoregulation and the ability of p53 to induce apoptosis for GBM was researched in the GBM tumor model...
January 9, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29317703/modeling-tumor-immunity-of-mouse-glioblastoma-by-exhausted-cd8-t-cells
#2
Hiroshi Nakashima, Quazim A Alayo, Pablo Penaloza-MacMaster, Gordon J Freeman, Vijay K Kuchroo, David A Reardon, Soledad Fernandez, Michael Caligiuri, E Antonio Chiocca
T cell exhaustion occurs during chronic infection and cancers. Programmed cell death protein-1 (PD-1) is a major inhibitory checkpoint receptor involved in T cell exhaustion. Blocking antibodies (Abs) against PD-1 or its ligand, PD-L1, have been shown to reverse T cell exhaustion during chronic infection and cancers, leading to improved control of persistent antigen. However, modeling tumor-specific T cell responses in mouse has been difficult due to the lack of reagents to detect and phenotype tumor-specific immune responses...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29313975/near-infrared-photoimmunotherapy-targeting-egfr-shedding-new-light-on-glioblastoma-treatment
#3
Thomas A Burley, Justyna Mączyńska, Anant Shah, Wojciech Szopa, Kevin J Harrington, Jessica K R Boult, Anna Mrozek-Wilczkiewicz, Maria Vinci, Jeffrey C Bamber, Wojciech Kaspera, Gabriela Kramer-Marek
Glioblastomas (GBM) are high-grade brain tumours, differentially driven by alterations (amplification, deletion, or missense mutations) in the epidermal growth factor receptor (EGFR), that carry a poor prognosis of just 12-15 months following standard therapy. A combination of interventions targeting tumor-specific cell surface regulators along with convergent downstream signalling pathways may enhance treatment efficacy. Against this background, we investigated a novel photoimmunotherapy approach combining the cytotoxicity of photodynamic therapy with the specificity of immunotherapy...
January 5, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29302887/analysis-of-immunobiologic-markers-in-primary-and-recurrent-glioblastoma
#4
Maryam Rahman, Jesse Kresak, Changlin Yang, Jianping Huang, Wesley Hiser, Paul Kubilis, Duane Mitchell
Glioblastoma (GBM) generates a varied immune response and understanding the immune microenvironment may lead to novel immunotherapy treatments modalities. The goal of this study was to evaluate the expression of immunologic markers of potential clinical significance in primary versus recurrent GBM and assess the relationship between these markers and molecular characteristics of GBM. Human GBM samples were evaluated and analyzed with immunohistochemistry for multiple immunobiologic markers (CD3, CD8, FoxP3, CD68, CD163, PD1, PDL1, CTLA4, CD70)...
January 4, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29290950/human-fibulin-3-protein-variant-expresses-anti-cancer-effects-in-the-malignant-glioma-extracellular-compartment-in-intracranial-xenograft-models
#5
Yanyan Li, Yuan Hu, Chuanjin Liu, Qingyue Wang, Xiaoxiao Han, Yong Han, Xue-Shun Xie, Xiong-Hui Chen, Xiang Li, Eric R Siegel, Kambiz Afrasiabi, Mark E Linskey, You-Xin Zhou, Yi-Hong Zhou
Background: Decades of cytotoxic and more recently immunotherapy treatments for malignant glioma have had limited success due to dynamic intra-tumoral heterogeneity. The dynamic interplay of cancer cell subpopulations has been found to be under the control of proteins in the cancer microenvironment. EGF-containing fibulin-like extracellular matrix protein (EFEMP1) (also fibulin-3) has the multiple functions of suppressing cancer growth and angiogenesis, while promoting cancer cell invasion...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29278673/immunotherapy-for-glioblastoma-on-the-sidelines-or-in-the-game
#6
David A Reardon, Kai Wucherpfennig, E Antonio Chiocca
The successful eradication of multiple tumor types, often in a durable manner, has recently validated the bona fide potential of an effectively mobilized immune response as a cancer therapy. Critical questions at present, therefore, include deciphering why some patients respond while others do not, as well as why certain cancers respond while others like glioblastoma do not. Glioblastoma remains a major unmet need in medical oncology and is considered incurable with less than 10% of patients surviving five years from diagnosis...
November 2017: Discovery Medicine
https://www.readbyqxmd.com/read/29242608/immunotherapies-for-malignant-glioma
#7
REVIEW
Vassiliki A Boussiotis, Alain Charest
Glioblastoma multiforme (GBM) is a highly malignant primary brain cancer with a dreadful overall survival and for which treatment options are limited. Recent breakthroughs in novel immune-related treatment strategies for cancer have spurred interests in usurping the power of the patient's immune system to recognize and eliminate GBM. Here, we discuss the unique properties of GBM's tumor microenvironment, the effects of GBM standard on care therapy on tumor-associated immune cells, and review several approaches aimed at therapeutically targeting the immune system for GBM treatment...
December 15, 2017: Oncogene
https://www.readbyqxmd.com/read/29222400/nkg2d-based-car-t-cells-and-radiotherapy-exert-synergistic-efficacy-in-glioblastoma
#8
Tobias Weiss, Michael Weller, Matthias Guckenberger, Charles L Sentman, Patrick Roth
Chimeric antigen receptor (CAR) T cell therapy is an emerging immunotherapy against several malignancies including glioblastoma, the most common and most aggressive malignant primary brain tumor in adults. The challenges in solid tumor immunotherapy comprise heterogenously expressed tumor target antigens and restricted trafficking of CAR T cells to and impaired long-term persistence at the tumor site, as well as the unaddressed integration of CAR T cell therapy into conventional anti-cancer treatments. We addressed these questions using a NKG2D-based chimeric antigen receptor construct (chNKG2D) in fully immunocompetent orthotopic glioblastoma mouse models...
December 8, 2017: Cancer Research
https://www.readbyqxmd.com/read/29213157/immunotherapy-and-gene-therapy-as-novel-treatments-for-cancer
#9
REVIEW
Martha Montserrat Rangel-Sosa, Estuardo Aguilar-Córdova, Augusto Rojas-Martínez
The immune system interacts closely with tumors during the disease development and progression to metastasis. The complex communication between the immune system and the tumor cells can prevent or promote tumor growth. New therapeutic approaches harnessing protective immunological mechanisms have recently shown very promising results. This is performed by blocking inhibitory signals or by activating immunological effector cells directly. Immune checkpoint blockade with monoclonal antibodies directed against the inhibitory immune receptors CTLA-4 and PD-1 has emerged as a successful treatment approach for patients with advanced melanoma...
September 30, 2017: Colombia Médica: CM
https://www.readbyqxmd.com/read/29209782/advances-in-immunotherapeutic-research-for-glioma-therapy
#10
REVIEW
Jeremy Tetsuo Miyauchi, Stella E Tsirka
Gliomas are primary malignancies of the brain. Tumors are staged based on malignancy, nuclear atypia, and infiltration of the surrounding brain parenchyma. Tumors are often diagnosed once patients become symptomatic, at which time the lesion is sizable. Glioblastoma (grade IV glioma) is highly aggressive and difficult to treat. Most tumors are diagnosed de novo. The gold standard of therapy, implemented over a decade ago, consists of fractionated radiotherapy and temozolomide, but unfortunately, chemotherapeutic resistance arises...
December 5, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/29200110/high-grade-gliomas
#11
Lakshmi Nayak, David A Reardon
PURPOSE OF REVIEW: This article reviews the standard treatment for high-grade gliomas, with a focus on promising new strategies and response assessment. RECENT FINDINGS: The new World Health Organization (WHO) classification of central nervous system tumors classifies high-grade gliomas based on molecular markers that are of prognostic and therapeutic significance. The addition of chemotherapy, specifically procarbazine, CCNU (lomustine), and vincristine, to radiation in newly diagnosed 1p/19q codeleted anaplastic oligodendrogliomas doubled overall survival...
December 2017: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/29190492/determinants-for-effective-alecsat-immunotherapy-treatment-on-autologous-patient-derived-glioblastoma-stem-cells
#12
Anna Wenger, Katja Werlenius, Alexander Hallner, Fredrik Bergh Thorén, Dan Farahmand, Magnus Tisell, Anja Smits, Bertil Rydenhag, Asgeir S Jakola, Helena Carén
Glioblastoma (GBM) is the most aggressive primary brain tumor with a median survival of less than 15 months, emphasizing the need for better treatments. Immunotherapy as a treatment for improving or aiding the patient's own immune defense to target the tumor has been suggested for GBM. A randomized clinical trial of adoptive cell transfer using ALECSAT (Autologous Lymphoid Effector Cells Specific Against Tumor Cells) is currently ongoing in Sweden. Here we performed a paired pre-clinical study to investigate the composition and in vitro effect of ALECSAT and identify determinants for the effect using autologous GBM-derived cancer stem cells (CSC), immunocytochemistry and flow cytometry...
November 27, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29168083/analysis-of-the-cancer-genome-atlas-tcga-database-identifies-an-inverse-relationship-between-interleukin-13-receptor-%C3%AE-1-and-%C3%AE-2-gene-expression-and-poor-prognosis-and-drug-resistance-in-subjects-with-glioblastoma-multiforme
#13
Jing Han, Raj K Puri
Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. A variety of targeted agents are being tested in the clinic including cancer vaccines, immunotoxins, antibodies and T cell immunotherapy for GBM. We have previously reported that IL-13 receptor subunits α1 and α2 of IL-13R complex are overexpressed in GBM. We are investigating the significance of IL-13Rα1 and α2 expression in GBM tumors. In order to elucidate a possible relationship between IL-13Rα1 and α2 expression with severity and prognoses of subjects with GBM, we analyzed gene expression (by microarray) and clinical data available at the public The Cancer Genome Atlas (TCGA) database (Currently known as Global Data Commons)...
November 22, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29167820/engineering-chimeric-antigen-receptor-t-cells-to-treat-glioblastoma
#14
Bryan D Choi, Donald M O'Rourke, Marcela V Maus
Immunotherapy has emerged as a promising strategy for glioblastoma (GBM), a disease that remains universally fatal despite currently available standard-of-care. Adoptive T cell therapy has been shown to produce potent antitumor immunity while obviating the need for traditional antigen presentation and primary immune responses. Chimeric antigen receptors (CARs) are specialized molecules that can be expressed on the surface of T cells allowing for redirected cytotoxicity against tumor antigens of interest. To date, the application of CAR T cells for GBM has been relatively limited, in large part due to a dearth of well-described tumor specific antigens that are both homogenously and frequently expressed...
August 2017: Journal of Targeted Therapies in Cancer
https://www.readbyqxmd.com/read/29162646/nkg2d-dependent-anti-tumor-effects-of-chemotherapy-and-radiotherapy-against-glioblastoma
#15
Tobias Weiss, Hannah Schneider, Manuela Silginer, Alexander Steinle, Martin N Pruschy, Bojan Polic, Michael Weller, Patrick Roth
PURPOSE: NKG2D is a potent activating immune cell receptor and glioma cells express the cognate ligands (NKG2DL). These ligands are inducible by cellular stress and temozolomide (TMZ) or irradiation (IR), the standard treatment of glioblastoma, could affect their expression. However, a role of NKG2DL for the efficacy of TMZ and IR has never been addressed. EXPERIMENTAL DESIGN: We assessed the effect of TMZ and IR on NKG2DL in vitro and in vivo in a variety of murine and human glioblastoma models including glioma-initiating cells and a cohort of paired glioblastoma samples from patients before and after therapy...
November 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29147863/prognostic-relevance-of-programmed-cell-death-ligand-1-expression-in-glioblastoma
#16
Kyu Sang Lee, Kyoungyul Lee, Sumi Yun, Seyoung Moon, Yujun Park, Jung Ho Han, Chae-Yong Kim, Hye Seung Lee, Gheeyoung Choe
The aim of this study was to determine the clinicopathological significance of programmed cell death ligand 1 (PD-L1) expression in glioblastoma (GBM). In a retrospective cohort of 115 consecutive patients with GBM, PD-L1 expression was determined using immunohistochemistry (IHC). Membranous and fibrillary PD-L1 staining of any intensity in > 5% neoplastic cells and tumour infiltrating immune cells (TIIs) was considered positive staining. In addition, isocitrate dehydrogenase-1 (IDH-1) (R132H) expression and cluster of differentiation 3 (CD3)-positive T-cell infiltration were investigated using IHC...
November 16, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29147621/in-depth-immunophenotyping-of-patients-with-glioblastoma-multiforme-impact-of-steroid-treatment
#17
Guranda Chitadze, Charlotte Flüh, Elgar Susanne Quabius, Sandra Freitag-Wolf, Christian Peters, Marcus Lettau, Jaydeep Bhat, Daniela Wesch, Hans-Heinrich Oberg, Stefanie Luecke, Ottmar Janssen, Michael Synowitz, Janka Held-Feindt, Dieter Kabelitz
Despite aggressive treatment regimens based on surgery and radiochemotherapy, the prognosis of patients with grade IV glioblastoma multiforme (GBM) remains extremely poor, calling for alternative options such as immunotherapy. Immunological mechanisms including the Natural Killer Group 2 member D (NKG2D) receptor-ligand system play an important role in tumor immune surveillance and targeting the NKG2D system might be beneficial. However, before considering any kind of immunotherapy, a precise characterization of the immune system is important, particularly in GBM patients where conventional therapies with impact on the immune system are frequently co-administered...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29106665/nivolumab-with-or-without-ipilimumab-in-patients-with-recurrent-glioblastoma-results-from-exploratory-phase-1-cohorts-of-checkmate-143
#18
Antonio Omuro, Gordana Vlahovic, Michael Lim, Solmaz Sahebjam, Joachim Baehring, Timothy Cloughesy, Alfredo Voloschin, Shakti H Ramkissoon, Keith L Ligon, Robert Latek, Ricardo Zwirtes, Lewis Strauss, Prashni Paliwal, Christopher T Harbison, David A Reardon, John H Sampsonc
Background: Immunotherapies have demonstrated efficacy across a diverse set of tumors supporting further evaluation in glioblastoma. The objective of this study was to evaluate the safety/tolerability and describe immune-mediated effects of nivolumab ± ipilimumab in patients with recurrent glioblastoma. Exploratory efficacy outcomes are also reported. Methods: Patients were randomized to receive nivolumab 3 mg/kg every 2 weeks (Q2W; NIVO3) or nivolumab 1 mg/kg + ipilimumab 3 mg/kg every 3 weeks (Q3W) for 4 doses, then nivolumab 3 mg/kg Q2W (NIVO1+IPI3)...
October 28, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29103912/optimization-of-il13r%C3%AE-2-targeted-chimeric-antigen-receptor-t-cells-for-improved-anti-tumor-efficacy-against-glioblastoma
#19
Christine E Brown, Brenda Aguilar, Renate Starr, Xin Yang, Wen-Chung Chang, Lihong Weng, Brenda Chang, Aniee Sarkissian, Alfonso Brito, James F Sanchez, Julie R Ostberg, Massimo D'Apuzzo, Behnam Badie, Michael E Barish, Stephen J Forman
T cell immunotherapy is emerging as a powerful strategy to treat cancer and may improve outcomes for patients with glioblastoma (GBM). We have developed a chimeric antigen receptor (CAR) T cell immunotherapy targeting IL-13 receptor α2 (IL13Rα2) for the treatment of GBM. Here, we describe the optimization of IL13Rα2-targeted CAR T cells, including the design of a 4-1BB (CD137) co-stimulatory CAR (IL13BBζ) and a manufacturing platform using enriched central memory T cells. Utilizing orthotopic human GBM models with patient-derived tumor sphere lines in NSG mice, we found that IL13BBζ-CAR T cells improved anti-tumor activity and T cell persistence as compared to first-generation IL13ζ-CAR CD8(+) T cells that had shown evidence for bioactivity in patients...
October 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29093005/dendritic-cells-enhance-polyfunctionality-of-adoptively-transferred-t-cells-which-target-cytomegalovirus-in-glioblastoma
#20
Elizabeth Reap, Carter M Suryadevara, Kristen A Batich, Luis Sanchez-Perez, Gary E Archer, Robert J Schmittling, Pamela K Norberg, James E Herndon, Patrick Healy, Kendra L Congdon, Patrick C Gedeon, Olivia C Campbell, Adam M Swartz, Katherine A Riccione, John S Yi, Mohammed K Hossain-Ibrahim, Anirudh Saraswathula, Smita K Nair, Anastasie M Dunn-Pirio, Taylor M Broome, Kent J Weinhold, Annick Desjardins, Gordana Vlahovic, Roger Mclendon, Allan H Friedman, Henry S Friedman, Darell D Bigner, Peter E Fecci, Duane A Mitchell, John H Sampson
Median survival for glioblastoma (GBM) remains <15 months. Human Cytomegalovirus (CMV) antigens have been identified in GBM but not normal brain, providing an unparalleled opportunity to subvert CMV antigens as tumor-specific immunotherapy targets. A recent trial in recurrent GBM patients demonstrated the potential clinical benefit of adoptive T cell therapy (ATCT) of CMV phosphoprotein 65 (pp65)-specific T cells. However, ex vivo analyses from this study found no change in the capacity of CMV pp65-specific T cells to gain multiple effector functions or polyfunctionality, which has been associated with superior antitumor efficacy...
November 1, 2017: Cancer Research
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