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glioblastoma immunotherapy

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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
#1
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
https://www.readbyqxmd.com/read/28441372/assessing-response-of-high-grade-gliomas-to-immune-checkpoint-inhibitors
#2
Solmaz Sahebjam, Dexter G Stallworth, Sepideh Mokhtari, Nam D Tran, John A Arrington
BACKGROUND: Immunotherapeutic agents, especially checkpoint inhibitors, have emerged as the mainstay of therapy for several solid and hematological malignancies. These therapies are under investigation for the treatment of high-grade gliomas and brain metastases. METHODS: This article reviews the unique challenges encountered when evaluating changes on magnetic resonance imaging (MRI) of glioblastomas seen in response to immunotherapy and checkpoint inhibitors and how to effectively incorporate MRI findings into the response assessment of high-grade gliomas to these emerging therapies...
April 2017: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/28438066/angiogenesis-inhibitors-in-tackling-recurrent-glioblastoma
#3
Thomas Hundsberger, David A Reardon, Patrick Y Wen
Despite aggressive multimodality treatment of glioblastoma, outcome remains poor and patients mostly die of local recurrences. Besides reoperation and occasionally reirradiation, systemic treatment of recurrent glioblastoma consists of alkylating chemotherapy (lomustine, temozolomide), bevacizumab and combinations thereof. Unfortunately, antiangiogenic agents failed to improve survival either as a monotherapy or in combination treatments. This review provides current insights into tumor-derived escape mechanisms and other areas of treatment failure of antiangiogenic agents in glioblastoma...
April 24, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28417936/oncolytic-alphaviruses-in-cancer-immunotherapy
#4
REVIEW
Kenneth Lundstrom
Oncolytic viruses show specific targeting and killing of tumor cells and therefore provide attractive assets for cancer immunotherapy. In parallel to oncolytic viral vectors based on adenoviruses and herpes simplex viruses, oncolytic RNA viruses and particularly alphaviruses have been evaluated as delivery vehicles. Immunization studies in experimental rodent models for various cancers including glioblastoma, hematologic, hepatocellular, colon, cervix, and lung cancer as well as melanoma have been conducted with naturally occurring oncolytic alphavirus strains such as M1 and Sindbis AR339...
April 12, 2017: Vaccines
https://www.readbyqxmd.com/read/28412740/combination-epidermal-growth-factor-receptor-variant-iii-peptide-pulsed-dendritic-cell-vaccine-with-mir-326-results-in-enhanced-killing-on-egfrviii-positive-cells
#5
Jianlong Li, Feng Wang, Guangzhi Wang, Ying Sun, Jinquan Cai, Xing Liu, Junhe Zhang, Xiaoyan Lu, Yongli Li, Meng Chen, Lingchao Chen, Chuanlu Jiang
The mutant Type III variant of epidermal growth factor receptor (EGFRvIII) is present in approximately one-third of glioblastoma (GBM) patients. It is never found in normal tissues; therefore, it represents a candidate target for GBM immunotherapy. PEPvIII, a peptide sequence from EGFRvIII, was designed to represent a target of glioma and is presented by MHC I/II complexes. Dendritic cells (DCs) have great potential to sensitize CD4+ T and CD8+ T cells to precisely target and eradicate GBM. Here, we show that PEPvIII could be loaded by DCs and presented to T lymphocytes, especially PEPvIII-specific CTLs, to precisely kill U87-EGFRvIII cells...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410300/applied-cancer-immunogenomics-leveraging-neoantigen-discovery-in-glioblastoma
#6
Tanner M Johanns, Gavin P Dunn
Glioblastoma (GBM) remains a significant cause of cancer-related mortality in pediatric and adult patients with limited treatment options. Immunotherapy represents a promising new therapeutic approach in many solid and hematologic malignancies, including GBM, although only a subset of patients responds clinically. Thus, current efforts are focused on identifying patients most likely to benefit from immune-based therapies. The cancer immunogenomics approach identifies candidate neoantigens from genomics information and represents a potentially exciting new space in precision neuro-oncology...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28389997/tumor-vaccines-for-malignant-gliomas
#7
REVIEW
Visish M Srinivasan, Sherise D Ferguson, Sungho Lee, Shiao-Pei Weathers, Brittany C Parker Kerrigan, Amy B Heimberger
Despite continued research efforts, glioblastoma multiforme (GBM) remains the deadliest brain tumor. Immunotherapy offers a novel way to treat this disease, the genetic signature of which is not completely elucidated. Additionally, these tumors are known to induce immunosuppression in the surrounding tumor microenvironment via an array of mechanisms, making effective treatment all the more difficult. The immunotherapeutic strategy of using tumor vaccines offers a way to harness the activity of the host immune system to potentially control tumor progression...
April 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28382534/pseudoprogression-radionecrosis-inflammation-or-true-tumor-progression-challenges-associated-with-glioblastoma-response-assessment-in-an-evolving-therapeutic-landscape
#8
REVIEW
Benjamin M Ellingson, Caroline Chung, Whitney B Pope, Jerrold L Boxerman, Timothy J Kaufmann
The wide variety of treatment options that exist for glioblastoma, including surgery, ionizing radiation, anti-neoplastic chemotherapies, anti-angiogenic therapies, and active or passive immunotherapies, all may alter aspects of vascular permeability within the tumor and/or normal parenchyma. These alterations manifest as changes in the degree of contrast enhancement or T2-weighted signal hyperintensity on standard anatomic MRI scans, posing a potential challenge for accurate radiographic response assessment for identifying anti-tumor effects...
April 5, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28371827/mutational-burden-immune-checkpoint-expression-and-mismatch-repair-in-glioma-implications-for-immune-checkpoint-immunotherapy
#9
Tiffany R Hodges, Martina Ott, Joanne Xiu, Zoran Gatalica, Jeff Swensen, Shouhao Zhou, Jason T Huse, John de Groot, Shulin Li, Willem W Overwijk, David Spetzler, Amy B Heimberger
Background.: Despite a multiplicity of clinical trials testing immune checkpoint inhibitors, the frequency of expression of potential predictive biomarkers is unknown in glioma. Methods.: In this study, we profiled the frequency of shared biomarker phenotypes. To clarify the relationships among tumor mutational load (TML), mismatch repair (MMR), and immune checkpoint expression, we profiled patients with glioma (n = 327), including glioblastoma (GBM) (n = 198), whose samples had been submitted for analysis from 2009 to 2016...
March 24, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28368867/immunomodulation-for-glioblastoma
#10
David A Reardon, Patrick Y Wen, Kai W Wucherpfennig, John H Sampson
PURPOSE OF REVIEW: Immunotherapy has emerged as a cornerstone of modern oncology with regulatory approvals for a variety of immunotherapeutics being achieved for a spectrum of cancer indications. Nonetheless the role of these approaches for patients with glioblastoma (GBM), the most common and deadliest primary malignant brain neoplasm, remains unknown. In this review, we summarize the current status of clinical development for the major types of immunotherapeutics, including vaccines, cell-based therapies, and immune checkpoint modulators for GBM...
June 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28367234/differentiation-by-nk-cells-is-a-prerequisite-for-effective-targeting-of-cancer-stem-cells-poorly-differentiated-tumors-by-chemopreventive-and-chemotherapeutic-drugs
#11
Anna Karolina Kozlowska, Paytsar Topchyan, Kawaljit Kaur, Han-Ching Tseng, Antonia Teruel, Toru Hiraga, Anahid Jewett
Natural Killer (NK) cells target oral, pancreatic, lung, breast, glioblastoma and melanoma stem-like/poorly differentiated tumors. Differentiation of the abovementioned tumors with supernatants from split-anergized NK cells decreases their susceptibility to NK cells, but increases their sensitivity to cisplatin (CDDP)-mediated cell death. Breast and melanoma tumor cells with CD44 knockdown display enhanced susceptibility to NK cell-mediated lysis, potentially due to decreased differentiation. We also demonstrate that sulindac, a non-steroidal anti-inflammatory drug and a chemopreventive agent, not only limits the growth of oral tumor cells, but also aids in cancer cell elimination by NK cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28362548/immune-infiltration-of-tumor-microenvironment-following-immunotherapy-for-glioblastoma-multiforme
#12
Giannis Sokratous, Stavros Polyzoidis, Keyoumars Ashkan
BACKGROUND: Autologous dentritic cell immunotherapy has been proven effective in treating tumors outside the central nervous system. Current evidence from phase I and II trials suggest a similar efficacy for central nervous system tumors as well and that an active immune response against these tumors can be generated. OBJECTIVE: We aim to review the literature to identify the types of immune responses against gliomas found to be generated by dendritic cell vaccinations and the types of immune cells subsequently infiltrating the glioma microenvironment...
March 31, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28357913/current-update-of-adoptive-immunotherapy-using-cytokine-induced-killer-cells-to-eliminate-malignant-gliomas
#13
Je Il Ryu, Myung Hoon Han, Jin Hwan Cheong, Jae Min Kim, Choong Hyun Kim
The therapeutic outcome for those with malignant glioma is poor, even though diverse therapeutic modalities have been developed. Immunotherapy has emerged as a therapeutic approach for malignant gliomas, making it possible to selectively treat tumors while sparing normal tissue. Here, we review clinical trials of adoptive immunotherapy approaches for malignant gliomas. We also describe a clinical trial that examined the efficacy and safety of autologous cytokine-induced killer (CIK) cells along with concomitant chemoradiotherapy for newly diagnosed glioblastoma...
March 2017: Immunotherapy
https://www.readbyqxmd.com/read/28334886/glioblastoma-associated-microglia-and-macrophages-targets-for-therapies-to-improve-prognosis
#14
Candice C Poon, Susobhan Sarkar, V Wee Yong, John J P Kelly
Glioblastoma is the most common and most malignant primary adult human brain tumour. Diagnosis of glioblastoma carries a dismal prognosis. Treatment resistance and tumour recurrence are the result of both cancer cell proliferation and their interaction with the tumour microenvironment. A large proportion of the tumour microenvironment consists of an inflammatory infiltrate predominated by microglia and macrophages, which are thought to be subverted by glioblastoma cells for tumour growth. Thus, glioblastoma-associated microglia and macrophages are logical therapeutic targets...
February 4, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28332095/identification-of-t-cell-target-antigens-in-glioblastoma-stem-like-cells-using-an-integrated-proteomics-based-approach-in-patient-specimens
#15
Carmen Rapp, Rolf Warta, Slava Stamova, Ali Nowrouzi, Christoph Geisenberger, Zoltan Gal, Saskia Roesch, Steffen Dettling, Simone Juenger, Mariana Bucur, Christine Jungk, Philip DaoTrong, Rezvan Ahmadi, Felix Sahm, David Reuss, Valentina Fermi, Esther Herpel, Volker Eckstein, Niels Grabe, Christoph Schramm, Markus A Weigand, Juergen Debus, Andreas von Deimling, Andreas Unterberg, Amir Abdollahi, Philipp Beckhove, Christel Herold-Mende
Glioblastoma (GBM) is a highly aggressive brain tumor and still remains incurable. Among others, an immature subpopulation of self-renewing and therapy-resistant tumor cells-often referred to as glioblastoma stem-like cells (GSCs)-has been shown to contribute to disease recurrence. To target these cells personalized immunotherapy has gained a lot of interest, e.g. by reactivating pre-existing anti-tumor immune responses against GSC antigens. To identify T cell targets commonly presented by GSCs and their differentiated counterpart, we used a proteomics-based separation of GSC proteins in combination with a T cell activation assay...
March 22, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28302023/anti-egfrviii-chimeric-antigen-receptor-modified-t-cells-for-adoptive-cell-therapy-of-glioblastoma
#16
Pei-Pei Ren, Ming Li, Tian-Fang Li, Shuang-Yin Han
Glioblastoma (GBM) is one of the most devastating brain tumors with poor prognosis and high mortality. Although radical surgical treatment with subsequent radiation and chemotherapy can improve the survival, the efficacy of such regimens is insufficient because the GBM cells can spread and destroy normal brain structures. Moreover, these non-specific treatments may damage adjacent healthy brain tissue. It is thus imperative to develop novel therapies to precisely target invasive tumor cells without damaging normal tissues...
March 16, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28300714/biomarkers-and-immunotherapeutic-targets-in-glioblastoma
#17
REVIEW
Alice L Hung, Tomas Garzon-Muvdi, Michael Lim
Glioblastoma (GBM) is an aggressive central nervous system (CNS) cancer with poor prognosis despite maximal therapy. The recent advent of immunotherapy holds great promise for improving GBM survival and has already made great strides towards changing current management strategies. A diverse set of biomarkers has been implicated as immunotherapeutic targets and prognostic indicators in other cancers. Some of the more extensively studied examples include cytokines (IL-4, IL-13, and TGF-ß), checkpoint molecules (PD-1, CTLA-4, TIM-3, LAG-3, CD137, GITR, OX40), and growth/angiogenesis proteins (endoglin and EGFR)...
March 11, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28299344/advances-in-immunotherapy-for-glioblastoma-multiforme
#18
REVIEW
Boyuan Huang, Hongbo Zhang, Lijuan Gu, Bainxin Ye, Zhihong Jian, Creed Stary, Xiaoxing Xiong
Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. Patients with GBM have poor outcomes, even with the current gold-standard first-line treatment: maximal safe resection combined with radiotherapy and temozolomide chemotherapy. Accumulating evidence suggests that advances in antigen-specific cancer vaccines and immune checkpoint blockade in other advanced tumors may provide an appealing promise for immunotherapy in glioma. The future of therapy for GBM will likely incorporate a combinatorial, personalized approach, including current conventional treatments, active immunotherapeutics, plus agents targeting immunosuppressive checkpoints...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28293764/immune-checkpoint-inhibition-and-its-relationship-with-hypermutation-phenoytype-as-a-potential-treatment-for-glioblastoma
#19
REVIEW
Manohan Sinnadurai, Kerrie L McDonald
Glioblastoma (GBM) is the most common malignant brain tumour in adults. Current prognosis with standard treatment is poor. Immunotherapy is a new paradigm in tumour management. Specifically, recent advances in the field of immune checkpoint molecules have led to dramatic results in many cancers. Inhibition of one particular, programmed cell death-1 (PD-1) has recently been shown to be highly effective in melanoma and non-small cell lung cancer. There has also been recent data to suggest potential benefit in GBM...
March 14, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28287848/immunomodulating-and-immunoresistance-properties-of-cancer-initiating-cells-implications-for-the-clinical-success-of-immunotherapy
#20
REVIEW
Cristina Maccalli, Giorgio Parmiani, Soldano Ferrone
Cancer-initiating cells (CICs) represent a relatively rare subpopulation of cells endowed with self-renewal, stemness properties, tumorigenicity in immunodeficient mice, and resistance to standard therapies as well as to immunotherapy. Here, we review the biological and immunological characteristics of CICs with special focus on the immunomodulating mechanisms they utilize to escape from immunosurveillance. The recently developed immunotherapeutic strategies have yielded remarkable clinical results in many types of tumors, indicating that indeed a patient's immune system can mount an immune response, which is effective in controlling tumor growth...
April 2017: Immunological Investigations
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