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glioblastoma immunotherapy

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https://www.readbyqxmd.com/read/29771386/immunotherapy-in-cns-cancers-the-role-of-immune-cell-trafficking
#1
Nivedita M Ratnam, Mark R Gilbert, Amber J Giles
Glioblastoma (GBM) is a highly malignant CNS tumor with very poor survival despite intervention with conventional therapeutic strategies. Although the CNS is separated from the immune system by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), emerging evidence of immune surveillance and the selective infiltration of GBMs by immune suppressive cells indicates that there is breakdown or compromise of these physical barriers. This in turn offers hope that immunotherapy can be applied to specifically target and reduce tumor burden...
May 15, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29769344/efficient-delivery-of-hcmv-t-cell-antigens-by-attenuated-sendai-virus-vectors
#2
Richard Kiener, Markus Fleischmann, Marian Alexander Wiegand, Niels A W Lemmermann, Christiane Schwegler, Christine Kaufmann, Angelique Renzaho, Simone Thomas, Eva Felder, Hans Helmut Niller, Benedikt Asbach, Ralf Wagner
Human Cytomegalovirus (HCMV) represents a major cause of clinical complications during pregnancy as well as immunosuppression and the licensing of a protective HCMV vaccine remains an unmet global need. Herein, we designed and validated novel Sendai virus (SeV) vectors delivering T cell immunogens IE-1 and pp65. To enhance vector safety, we used a replication-deficient strain (rdSeV) that infects target cells in a non-productive manner while retaining viral gene expression. In this study, we explored the impact that transduction with rdSeV has on human dendritic cells (DCs) by comparing it to the parental, replication-competent Sendai virus strain (rcSeV) as well as the poxvirus strain Modified Vaccinia Ankara (MVA)...
May 16, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29769134/advances-on-chimeric-antigen-receptor-modified-t-cell-therapy-for-oncotherapy
#3
REVIEW
Yanyu Pang, Xiaoyang Hou, Chunsheng Yang, Yanqun Liu, Guan Jiang
Tumor treatment is still complicated in the field of medicine. Tumor immunotherapy has been the most interesting research field in cancer therapy. Application of chimeric antigen receptor T (CAR-T) cell therapy has recently achieved excellent clinical outcome in patients, especially those with CD19-positive hematologic malignancies. This phenomenon has induced intense interest to develop CAR-T cell therapy for cancer, especially for solid tumors. However, the performance of CAR-T cell treatment in solid tumor is not as satisfactory as that in hematologic disease...
May 16, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29764444/molecular-and-clinical-characterization-of-ptpn2-expression-from-rna-seq-data-of-996-brain-gliomas
#4
Peng-Fei Wang, Hong-Qing Cai, Chuan-Bao Zhang, Yan-Michael Li, Xiang Liu, Jing-Hai Wan, Tao Jiang, Shou-Wei Li, Chang-Xiang Yan
BACKGROUND: Immune checkpoint inhibitors have been shown to promote antitumor immunity and achieve durable tumor remissions. However, certain tumors are refractory to current immunotherapy. These negative results encouraged us to uncover other therapeutic targets and strategies. PTPN2 (protein tyrosine phosphatase, non-receptor type 2) has been newly identified as an immunotherapy target. Loss of PTPN2 sensitizes the tumor to immunotherapy via IFNγ signaling. METHODS: Here, we investigated the relationship between PTPN2 mRNA levels and clinical characteristics in gliomas...
May 15, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29755681/dendritic-cell-activation-enhances-anti-pd-1-mediated-immunotherapy-against-glioblastoma
#5
Tomas Garzon-Muvdi, Debebe Theodros, Andrew S Luksik, Russell Maxwell, Eileen Kim, Christopher M Jackson, Zineb Belcaid, Sudipto Ganguly, Betty Tyler, Henry Brem, Drew M Pardoll, Michael Lim
Introduction: The glioblastoma (GBM) immune microenvironment is highly suppressive as it targets and hinders multiple components of the immune system. Checkpoint blockade (CB) is being evaluated for GBM patients. However, biomarker analyses suggest that CB monotherapy may be effective only in a small fraction of GBM patients. We hypothesized that activation of antigen presentation would increase the therapeutic response to PD-1 blockade. Results: We show that activating DCs through TLR3 agonists enhances the anti-tumor immune response to CB and increases survival in GBM...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29754163/inhibition-of-autophagy-potentiated-the-anti-tumor-effects-of-vegf-and-cd47-bispecific-therapy-in-glioblastoma
#6
Xuyao Zhang, Shaofei Wang, Yanyang Nan, Jiajun Fan, Wei Chen, Jingyun Luan, Yichen Wang, Yanxu Liang, Song Li, Wenzhi Tian, Dianwen Ju
Glioblastoma, characterized by extensive microvascular proliferation and invasive tumor growth, is one of the most common and lethal malignancies in adults. Benefits of the conventional anti-angiogenic therapy were only observed in a subset of patients and limited by diverse relapse mechanism. Fortunately, recent advances in cancer immunotherapy have offered new hope for patients with glioblastoma. Herein, we reported a novel dual-targeting therapy for glioblastoma through simultaneous blockade of VEGF and CD47 signaling...
May 12, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29733389/temozolomide-for-immunomodulation-in-the-treatment-of-glioblastoma
#7
Aida Karachi, Farhad Dastmalchi, Duane Mitchell, Maryam Rahman
Temozolomide is the most widely used chemotherapy for patients with glioblastoma (GBM) despite the fact that approximately half of treated patients have temozolomide resistance and all patients eventually fail therapy. Due to the limited efficacy of existing therapies, immunotherapy is being widely investigated for patients with GBM. However, initial immunotherapy trials in GBM patients have had disappointing results as monotherapy. Therefore, combinatorial treatment strategies are being investigated. Temozolomide has several effects on the immune system that are dependent on mode of delivery and the dosing strategy that may have unpredicted effects on immunotherapy...
May 4, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29731959/identification-of-neoepitopes-recognized-by-tumor-infiltrating-lymphocytes-tils-from-patients-with-glioma
#8
Davide Valentini, Martin Rao, Qingda Meng, Anna von Landenberg, Jiri Bartek, Georges Sinclair, Georgia Paraschoudi, Elke Jäger, Inti Harvey-Peredo, Ernest Dodoo, Markus Maeurer
Neoepitope-specific T-cell responses have been shown to induce durable clinical responses in patients with advanced cancers. We explored the recognition patterns of tumor-infiltrating T lymphocytes (TILs) from patients with glioblastoma multiforme (GBM), the most fatal form of tumors of the central nervous system. Whole-genome sequencing was used for generating DNA sequences representing the entire spectrum of 'private' somatic mutations in GBM tumors from five patients, followed by 15-mer peptide prediction and subsequent peptide synthesis...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29721184/correlation-between-lower-balance-of-th2-helper-t-cells-and-expression-of-pd-l1-pd-1-axis-genes-enables-prognostic-prediction-in-patients-with-glioblastoma
#9
Yasuo Takashima, Atsushi Kawaguchi, Tomohiko Kanayama, Azusa Hayano, Ryuya Yamanaka
Common cancer treatments include radiation therapy, chemotherapy including molecular targeted drugs and anticancer drugs, and surgical treatment. Recent studies have focused on investigating the mechanisms by which immune cells attack cancer cells and produce immune tolerance-suppressing cytokines, as well as on their potential application in cancer immunotherapy. We conducted expression profiling of CD274 ( PD-L1 ), GATA3, IFNG, IL12R, IL12RB2, IL4, PDCD1 ( PD-1 ), PDCD1LG2 ( PD-L2 ), and TBX21 ( T-bet ) using data of 158 glioblastoma multiforme (GBM) patients with clinical information available at The Cancer Genome Atlas...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29696949/overview-on-current-treatment-standards-in-high-grade-gliomas
#10
Alessia Pellerino, Federica Franchino, Riccardo Soffietti, Roberta Rudà
High-grade gliomas (HGGs) are the most common primary tumors of the Central Nervous System, which include anaplastic gliomas (grade III) and glioblastomas (GBM, grade IV). Surgery is the mainstay of treatment in HGGs in order to achieve a histological and molecular characterization, as well as relieve neurological symptoms and improve seizure control. Combinations of some molecular factors, such as IDH 1-2 mutations, 1p/19q codeletion and MGMT methylation status, allow to classify different subtypes of gliomas and identify patients with different outcome...
April 26, 2018: Quarterly Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29692957/novel-immunotherapeutics-for-the-treatment-of-glioblastoma-the-last-decade-of-research
#11
REVIEW
Emaad M Khansur, Ashish H Shah, Kyle Lacy, Manish Kuchakulla, Ricardo J Komotar
Despite surgical resection and adjuvant chemoradiation, survival for glioblastoma remains poor. Because of the dismal prognosis, attention has shifted to alternative adjuvant treatment modalities. Although traditionally limited to systemic malignancies (melanoma, lung and colon cancer), the field of immunotherapy has recently identified glioblastoma as a potential target for new treatments. Anti-tumor vaccines (dendritic cell/heat shock), checkpoint inhibitors, chimeric T-cell receptors, and virotherapy all have been preliminarily trialed in glioblastoma patients with reasonable success and safety...
January 30, 2018: Curēus
https://www.readbyqxmd.com/read/29691293/immunotherapy-for-glioblastoma-playing-chess-not-checkers
#12
Christopher M Jackson, Michael Lim
Patients with glioblastoma (GBM) exhibit a complex state of immune dysfunction involving multiple mechanisms of local, regional, and systemic immune suppression and tolerance. These pathways are now being identified and their relative contributions explored. Delineating how these pathways are interrelated is paramount to effectively implementing immunotherapy for GBM.
April 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29688039/mathematical-modelling-of-the-synergistic-combination-of-radiotherapy-and-indoleamine-2-3-dioxygenase-ido-inhibitory-immunotherapy-against-glioblastoma
#13
Arthur Chakwizira, Jonatan Ahlstedt, Henrietta Nittby Redebrandt, Crister Ceberg
OBJECTIVE: Recent research has shown that combining radiotherapy and immunotherapy can counteract the ability of cancer to evade and suppress the native immune system. To optimize the synergy of the combined therapies, factors such as radiation dose and fractionation must be considered, alongside numerous parameters resulting from the complexity of cancer-immune system interactions. It is instructive to use mathematical models to tackle this problem. METHODS: In this work, we adapted a model primarily to describe the synergistic effect between single-fraction radiotherapy and immunotherapy (1-methyl tryptophan) observed in previous experiments with glioblastoma-carrying rats...
April 24, 2018: British Journal of Radiology
https://www.readbyqxmd.com/read/29683891/il-21-increases-the-reactivity-of-allogeneic-human-v%C3%AE-9v%C3%AE-2-t-cells-against-primary-glioblastoma-tumors
#14
Noémie Joalland, Cynthia Chauvin, Lisa Oliver, François M Vallette, Claire Pecqueur, Ulrich Jarry, Emmanuel Scotet
Glioblastoma multiforme (GBM) remains the most frequent and deadliest primary brain tumor in adults despite aggressive treatments, because of the persistence of infiltrative and resistant tumor cells. Nonalloreactive human Vγ9Vδ2 T lymphocytes, the major peripheral γδ T-cell subset in adults, represent attractive effectors for designing immunotherapeutic strategies to track and eliminate brain tumor cells, with limited side effects. We analyzed the effects of ex vivo sensitizations of Vγ9Vδ2 T cells by IL-21, a modulating cytokine, on their cytolytic reactivity...
April 20, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29680243/therapeutic-monoclonal-antibodies-delivery-for-the-glioblastoma-treatment
#15
Flávia Sousa, Rui P Moura, Elias Moreira, Cláudia Martins, Bruno Sarmento
Glioblastoma multiforme (GBM) is the most common and challenging primary malignant brain tumor, being the median overall survival between 10 and 14 months due to its invasive characteristics. GBM treatment is mainly based on the maximal surgical resection and radiotherapy associated to chemotherapy. Monoclonal antibodies (mAbs) have been used in chemotherapy protocols for GBM treatment in order to improve immunotherapy and antiangiogenic processes. High specificity and affinity of mAbs for biological targets make them highly used for brain tumor therapy...
2018: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/29666934/quo-vadis-do-immunotherapies-have-a-role-in-glioblastoma
#16
REVIEW
Sylvia C Kurz, Patrick Y Wen
PURPOSE OF REVIEW: More effective therapies for glioblastoma are urgently needed. Immunotherapeutic strategies appear particularly promising and are therefore intensively studied. This article reviews the current understanding of the immunosuppressive glioblastoma microenvironment, discusses the rationale behind various immunotherapies, and outlines the findings of several recently published clinical studies. RECENT FINDINGS: The results of CheckMate-143 indicated that nivolumab is not superior to bevacizumab in patients with recurrent glioblastoma...
April 18, 2018: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/29651966/specific-cytostatic-and-cytotoxic-effect-of-dihydrochelerythrine-in-glioblastoma-cells-role-of-nf-kb-b-catenin-and-stat3-il-6-pathways
#17
Tereza Cristina Costa Silva, Noelio de Jesus Menezes-Filho, Giselle Pinto de Faria Lopes, Diego Madureira de Oliveira, Ezequiel Pereira, Bruno Penas Seara Pitanga, Eudes S Velozo, Songeli Menezes Freire, Jorge Clarencio de Souza Andrade, Helena Lobo Borges, Stevens Kastrup Rehen, Vivaldo Moura-Neto, Silvia Lima Costa
A glioblastoma is a primary CNS tumor that is more aggressive and lethal than other brain tumors. Its location, rapid proliferation, invasive growth, angiogenesis and immunosuppression are the main factors that limit its treatment, making it a major challenge to neuro-oncology. OBJECTIVE: This study investigated the in vitro effects of the alkaloid dihydrochelerythrine (DHC), which is extracted from Zanthoxylum stelligerum, on the viability, proliferation, cell death and b-catenin, NFkB, STAT3/pSTAT3 and interleukins roles...
April 12, 2018: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29651429/therapeutic-potential-of-thymoquinone-in-glioblastoma-treatment-targeting-major-gliomagenesis-signaling-pathways
#18
REVIEW
Fabliha Ahmed Chowdhury, Md Kamal Hossain, A G M Mostofa, Maruf Mohammad Akbor, Muhammad Shahdaat Bin Sayeed
Glioblastoma multiforme (GBM) is one of the most devastating brain tumors with median survival of one year and presents unique challenges to therapy because of its aggressive behavior. Current treatment strategy involves surgery, radiotherapy, immunotherapy, and adjuvant chemotherapy even though optimal management requires a multidisciplinary approach and knowledge of potential complications from both the disease and its treatment. Thymoquinone (TQ), the main bioactive component of Nigella sativa L., has exhibited anticancer effects in numerous preclinical studies...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29643764/the-idh1-mutation-induced-oncometabolite-2-hydroxyglutarate-may-affect-dna-methylation-and-expression-of-pd-l1-in-gliomas
#19
Luyan Mu, Yu Long, Changlin Yang, Linchun Jin, Haipeng Tao, Haitao Ge, Yifan E Chang, Aida Karachi, Paul S Kubilis, Gabriel De Leon, Jiping Qi, Elias J Sayour, Duane A Mitchell, Zhiguo Lin, Jianping Huang
Background: Malignant gliomas are heterogeneous brain tumors with the potential for aggressive disease progression, as influenced by suppressive immunoediting. Given the success and enhanced potential of immune-checkpoint inhibitors in immunotherapy, we focused on the connections between genetic alterations affected by IDH1 mutations and immunological landscape changes and PDL-1 expression in gliomas. Methods: Paired surgically resected tumors from lower-grade gliomas (LGGs) and glioblastomas (GBM) were investigated, and a genetic analysis of patients' primary tumor samples culled from TCGA datasets was performed...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29643471/current-state-of-immunotherapy-for-glioblastoma
#20
REVIEW
Michael Lim, Yuanxuan Xia, Chetan Bettegowda, Michael Weller
Glioma is the most common primary cancer of the central nervous system, and around 50% of patients present with the most aggressive form of the disease, glioblastoma. Conventional therapies, including surgery, radiotherapy, and pharmacotherapy (typically chemotherapy with temozolomide), have not resulted in major improvements in the survival outcomes of patients with glioblastoma. Reasons for this lack of progress include invasive tumour growth in an essential organ, which limits the utility of local therapy, as well as the protection of tumour cells by the blood-brain barrier, their intrinsic resistance to the induction of cell death, and lack of dependence on single, targetable oncogenic pathways, all of which impose challenges for systemic therapy...
April 11, 2018: Nature Reviews. Clinical Oncology
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