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glioblastoma immunotherapy

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https://www.readbyqxmd.com/read/28640704/immunotherapy-for-brain-tumors
#1
John H Sampson, Marcela V Maus, Carl H June
Glioblastoma (GBM) is the most lethal form of brain tumor and remains a large, unmet medical need. This review focuses on recent advances in the neurosciences that converge with the broader field of immuno-oncology. Recent findings in neuroanatomy provide a basis for new approaches of cellular therapies for tumors that involve the CNS. The ultimate success of immunotherapy in the CNS will require improved imaging technologies and methods for analysis of the tumor microenvironment in patients with GBM. It is likely that combinatorial approaches with targeted immunotherapies will be required to exploit the vulnerabilities of GBM and other brain tumors...
June 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28583430/the-egfr-variant-iii-mutant-as-a-target-for-immunotherapy-of-glioblastoma-multiforme
#2
REVIEW
Dimitry A Chistiakov, Ivan V Chekhonin, Vladimir P Chekhonin
In epithelial tumors, the epidermal growth factor receptor (EGFR) controls key signaling pathways responsible for growth, proliferation, migration, and survival of tumor cells. The epidermal growth factor receptor variant III (EGFRvIII) is the most common EGFR mutation that occurs in up to 30% of high-grade gliomas especially glioblastoma multiforme (GBM). EGFRvIII arises from the deletion of exon 2-7 that leads to the formation of the constitutively activated mutant receptor incapable of binding any known ligand...
June 2, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28574813/an-immunocompetent-mouse-model-of-human-glioblastoma
#3
Samantha Semenkow, Shen Li, Ulf D Kahlert, Eric H Raabe, Jiadi Xu, Antje Arnold, Miroslaw Janowski, Byoung Chol Oh, Gerald Brandacher, Jeff W M Bulte, Charles G Eberhart, Piotr Walczak
Orthotopic xenotransplantation studies represent the final stage in preclinical cancer research and could facilitate the implementation of precision medicine. To date, these xenografts have been tested in immunodeficient animals, but complete elimination of the adaptive immunity is a significant drawback. We present a method of efficient human glioblastoma (GBM) cell engraftment in adult mice with intact immune systems, mediated by a transient blockade of T-cell co-stimulation. Compared to transplants grown in immunodeficient hosts, the resulting tumors more accurately resemble the clinical pathophysiology of patient GBMs, which are characterized by blood-brain-barrier leakage and strong neo-vascularization...
May 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28567588/immunotherapy-and-radiation-in-glioblastoma
#4
REVIEW
Solmaz Sahebjam, Andrew Sharabi, Michael Lim, Pravin Kesarwani, Prakash Chinnaiyan
Radiation therapy plays a central role in the management of glioblastoma. Although primarily thought of as modality to provide local tumor control through DNA damage, the capacity of ionizing radiation to modulate tumor immune response has long been recognized. The recent emergence of clinically active immunotherapies offers exciting potential for harnessing the immune modulatory effects or radiation through combinatorial strategies designed to enhance clinical outcomes. In this Review, we provide background describing the unique immune environment within the central nervous system, how ionizing radiation may modulate the tumor immune response, preclinical and clinical data testing the combination of radiation and immune modulating agents, and highlight some of the current challenges in extending these findings clinically...
May 31, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28564668/updates-on-chimeric-antigen-receptor-mediated-glioblastoma-immunotherapy
#5
George Mao, Prakash Sampath, Sadhak Sengupta
Glioblastoma multiforme (GBM) is the most malignant of the primary central nervous system (CNS) neoplasms, accounting for nearly 80% of all primary brain tumors and is associated with high morbidity and mortality. Immunotherapy is proving to be a fertile ground for next-generation GBM therapy, with large translational research projects and clinical trials currently underway. One particularly promising area is the chimeric antigen receptors (CARs) in the context of lymphocyte adoptive cell therapy (ACT), which has achieved success in the treatment of hematological malignancies...
June 1, 2017: Rhode Island Medical Journal
https://www.readbyqxmd.com/read/28554666/human-cytomegalovirus-mediated-immunomodulation-effects-on-glioblastoma-progression
#6
REVIEW
Haidn Foster, Ilya V Ulasov, Charles S Cobbs
The presence of human cytomegalovirus (HCMV) and glioblastoma multiforme (GBM), first established in 2002, has developed into an area of considerable interest and controversy. Numerous studies have found evidence of possible HCMV infection of GBM tumor cells as well as myriad onco- and immunomodulatory properties exhibited by HCMV antigens and transcripts, while recent reports have failed to detect HCMV particles in GBM and question the virus' role in tumor progression. This review highlights the known immunomodulatory properties of HCMV, independent of GBM infection status, that help drive the virus from peripheral blood into the vital tissues and subsequently dampen local immune response, assisting GBM tumors in evading immune surveillance and contributing to the disease's poor prognosis...
May 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28550091/transgenic-expression-of-il15-improves-antiglioma-activity-of-il13ralpha2-car-t-cells-but-results-in-antigen-loss-variants
#7
Giedre Krenciute, Brooke L Prinzing, Zhongzhen Yi, Meng-Fen Wu, Hao Liu, Gianpietro Dotti, Irina V Balyasnikova, Stephen Gottschalk
Glioblastoma (GBM) is the most aggressive primary brain tumor in adults and is virtually incurable with conventional therapies. Immunotherapy with T cells expressing GBM-specific chimeric antigen receptors (CARs) is an attractive approach to improve outcomes. Although CAR T cells targeting GBM antigens such as IL13Ralpha2 (interleukin 13 Receptor Subunit Alpha 2), HER2 (human epidermal growth factor receptor 2), and EGFRvIII (epidermal growth factor receptor variant III) have had antitumor activity in preclinical models, early phase clinical testing has demonstrated limited antiglioma activity...
May 26, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28544801/nanotherapeutic-systems-for-local-treatment-of-brain-tumors
#8
REVIEW
Rami Walid Chakroun, Pengcheng Zhang, Ran Lin, Paula Schiapparelli, Alfredo Quinones-Hinojosa, Honggang Cui
Malignant brain tumor, including the most common type glioblastoma, are histologically heterogeneous and invasive tumors known as the most devastating neoplasms with high morbidity and mortality. Despite multimodal treatment including surgery, radiotherapy, chemotherapy, and immunotherapy, the disease inevitably recurs and is fatal. This lack of curative options has motivated researchers to explore new treatment strategies and to develop new drug delivery systems (DDSs); however, the unique anatomical, physiological, and pathological features of brain tumors greatly limit the effectiveness of conventional chemotherapy...
May 24, 2017: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
https://www.readbyqxmd.com/read/28539528/prospect-of-immunotherapy-for-glioblastoma-tumor-vaccine-immune-checkpoint-inhibitors-and-combination-therapy
#9
Eiichi Ishikawa, Tetsuya Yamamoto, Akira Matsumura
To date, clinical trials of various vaccine therapies using autologous tumor antigens or tumor-associated/specific antigen peptide with adjuvants have been performed to treat patients with high-grade gliomas (HGG). Furthermore, immune checkpoint pathway-targeted therapies including anti- programmed cell death 1 (PD-1) antibody have been remarkably effective in other neoplasms, and various clinical trials with anti-PD-1 antibody in patients with HGG have started to date. It is possible that up-regulation of immune checkpoint molecules in tumor tissues after vaccine therapy may be one of the mechanisms of vaccine failure...
May 24, 2017: Neurologia Medico-chirurgica
https://www.readbyqxmd.com/read/28536525/immune-checkpoint-in-glioblastoma-promising-and-challenging
#10
REVIEW
Jing Huang, Fangkun Liu, Zhixiong Liu, Hui Tang, Haishan Wu, Qianni Gong, Jindong Chen
Glioblastoma (GBM) is a severe malignant brain cancer with poor overall survival. Conventional intervention remains dismal to prevent recurrence and deterioration of GBM cell. Recent years have witnessed exciting breakthroughs in novel immune strategies, especially checkpoint inhibitors, some of which have become adjuvant setting after standard of care in melanoma. Several clinical trials of checkpoint inhibitors are ongoing in glioblastoma and other brain carcinomas. Plus, synergistic combinations of checkpoint inhibitors with conventional therapy strategies-radiotherapy, temozolomide, bevacizumab, and corticosteroids are now being exploited and applied in clinical settings...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28529551/history-and-current-state-of-immunotherapy-in-glioma-and-brain-metastasis
#11
REVIEW
Tresa McGranahan, Gordon Li, Seema Nagpal
Malignant brain tumors such as glioblastoma (GBM) and brain metastasis have poor prognosis despite conventional therapies. Successful use of vaccines and checkpoint inhibitors in systemic malignancy has increased the hope that immune therapies could improve survival in patients with brain tumors. Manipulating the immune system to fight malignancy has a long history of both modest breakthroughs and pitfalls that should be considered when applying the current immunotherapy approaches to patients with brain tumors...
May 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28521700/glioblastoma-multiforme-diagnosis-and-treatment-recent-literature-review
#12
Ron Batash, Noam Asna, Pamela Schaffer, Nicole Francis, Moshe Schaffer
BACKGROUND: Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, with an incidence of 3.19 cases per 100,000 person years and remarkably poor prognosis showing a 5-year survival rate of 4-5%, and only a 26-33% survival rate at 2 years in clinical trials. OBJECTIVE: In this paper, we review the different types of treatment modalities based on the relevant databases. Methods of diagnosis will be described briefly. METHOD: Systemic compilation of the relevant literature...
May 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28514722/the-interventional-effect-of-new-drugs-combined-with-the-stupp-protocol-on-glioblastoma-a-network-meta-analysis
#13
Mei Li, Xiangqi Song, Jun Zhu, Aijun Fu, Jianmin Li, Tong Chen
OBJECTIVE: New therapeutic agents in combination with the standard Stupp protocol (a protocol about the temozolomide combined with radiotherapy treatment with glioblastoma was research by Stupp R in 2005) were assessed to evaluate whether they were superior to the Stupp protocol alone, to determine the optimum treatment regimen for patients with newly diagnosed glioblastoma. PATIENTS AND METHODS: We implemented a search strategy to identify studies in the following databases: PubMed, Cochrane Library, EMBASE, CNKI, CBM, Wanfang, and VIP, and assessed the quality of extracted data from the trials included...
May 11, 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28512646/mri-in-glioma-immunotherapy-evidence-pitfalls-and-perspectives
#14
REVIEW
Domenico Aquino, Andrea Gioppo, Gaetano Finocchiaro, Maria Grazia Bruzzone, Valeria Cuccarini
Pseudophenomena, that is, imaging alterations due to therapy rather than tumor evolution, have an important impact on the management of glioma patients and the results of clinical trials. RANO (response assessment in neurooncology) criteria, including conventional MRI (cMRI), addressed the issues of pseudoprogression after radiotherapy and concomitant chemotherapy and pseudoresponse during antiangiogenic therapy of glioblastomas (GBM) and other gliomas. The development of cancer immunotherapy forced the identification of further relevant response criteria, summarized by the iRANO working group in 2015...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28499389/a-phase-ii-trial-of-autologous-dendritic-cell-vaccination-and-radiochemotherapy-following-fluorescence-guided-surgery-in-newly-diagnosed-glioblastoma-patients
#15
Susana Inogés, Sonia Tejada, Ascensión López-Díaz de Cerio, Jaime Gállego Pérez-Larraya, Jaime Espinós, Miguel Angel Idoate, Pablo Daniel Domínguez, Reyes García de Eulate, Javier Aristu, Maurizio Bendandi, Fernando Pastor, Marta Alonso, Enrique Andreu, Felipe Prósper Cardoso, Ricardo Díez Valle
BACKGROUND: Prognosis of patients with glioblastoma multiforme (GBM) remains dismal, with median overall survival (OS) of about 15 months. It is therefore crucial to search alternative strategies that improve these results obtained with conventional treatments. In this context, immunotherapy seems to be a promising therapeutic option. We hypothesized that the addition of tumor lysate-pulsed autologous dendritic cells (DCs) vaccination to maximal safe resection followed by radiotherapy and concomitant and adjuvant temozolomide could improve patients' survival...
May 12, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28497804/vaccine-based-immunotherapeutic-approaches-to-gliomas-and-beyond
#16
REVIEW
Michael Weller, Patrick Roth, Matthias Preusser, Wolfgang Wick, David A Reardon, Michael Platten, John H Sampson
Astrocytic and oligodendroglial gliomas are intrinsic brain tumours characterized by infiltrative growth and resistance to classic cancer therapies, which renders them inevitably lethal. Glioblastoma, the most common type of glioma, also exhibits neoangiogenesis and profound immunosuppressive properties. Accordingly, strategies to revert glioma-associated immunosuppression and promote tumour-directed immune responses have been extensively explored in rodent models and in large clinical trials of tumour immunotherapy...
June 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28491282/cell-growth-inhibition-and-apoptotic-effects-of-a-specific-anti-rtfscfv-antibody-on-prostate-cancer-but-not-glioblastoma-cells
#17
Foroogh Nejatollahi, Payam Bayat, Bahareh Moazen
Background: Single chain antibody (scFv) has shown interesting results in cancer immunotargeting approaches, due to its advantages over monoclonal antibodies. Regeneration and tolerance factor (RTF) is one of the most important regulators of extracellular and intracellular pH in eukaryotic cells. In this study, the inhibitory effects of a specific anti-RTF scFv were investigated and compared between three types of prostate cancer and two types of glioblastoma cells.  Methods: A phage antibody display library of scFv was used to select specific scFvs against RTF using panning process...
2017: F1000Research
https://www.readbyqxmd.com/read/28488122/the-potential-of-cellular-and-viral-based-immunotherapies-for-malignant-glioma-dendritic-cell-vaccines-adoptive-cell-transfer-and-oncolytic-viruses
#18
REVIEW
Russell Maxwell, Andrew S Luksik, Tomas Garzon-Muvdi, Michael Lim
PURPOSE OF REVIEW: Malignant gliomas, including glioblastoma and anaplastic astrocytoma, are the most frequent primary brain tumors and present with many treatment challenges. In this review, we discuss the potential of cellular- and viral-based immunotherapies in the treatment of malignant glioma, specifically focusing on dendritic cell vaccines, adoptive cell therapy, and oncolytic viruses. RECENT FINDINGS: Diverse cellular- and viral-based strategies have been engineered and optimized to generate either a specific or broad antitumor immune response in malignant glioma...
June 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28450700/sensitization-of-glioblastoma-tumor-micro-environment-to-chemo-and-immunotherapy-by-galectin-1-intranasal-knock-down-strategy
#19
Matthias Van Woensel, Thomas Mathivet, Nathalie Wauthoz, Rémi Rosière, Abhishek D Garg, Patrizia Agostinis, Véronique Mathieu, Robert Kiss, Florence Lefranc, Louis Boon, Jochen Belmans, Stefaan W Van Gool, Holger Gerhardt, Karim Amighi, Steven De Vleeschouwer
In this study, we evaluated the consequences of reducing Galectin-1 (Gal-1) in the tumor micro-environment (TME) of glioblastoma multiforme (GBM), via nose-to-brain transport. Gal-1 is overexpressed in GBM and drives chemo- and immunotherapy resistance. To promote nose-to-brain transport, we designed siRNA targeting Gal-1 (siGal-1) loaded chitosan nanoparticles that silence Gal-1 in the TME. Intranasal siGal-1 delivery induces a remarkable switch in the TME composition, with reduced myeloid suppressor cells and regulatory T cells, and increased CD4+ and CD8+ T cells...
April 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28447277/assessment-of-pd-1-positive-cells-on-initial-and-secondary-resected-tumor-specimens-of-newly-diagnosed-glioblastoma-and-its-implications-on-patient-outcome
#20
Tsubasa Miyazaki, Eiichi Ishikawa, Masahide Matsuda, Hiroyoshi Akutsu, Satoru Osuka, Noriaki Sakamoto, Shingo Takano, Tetsuya Yamamoto, Koji Tsuboi, Akira Matsumura
Glioblastoma (GBM) is the most common type of malignant brain tumor and has a very poor prognosis. Most patients relapse within 12 months despite aggressive treatment and patient outcome after recurrent is extremely worse. This study was designed to clarify the change of the molecular expression, including programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), on the initial and secondary resected tumor specimens and to address the influence of these expressions for patient outcome after second surgery of glioblastoma...
April 26, 2017: Journal of Neuro-oncology
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