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https://read.qxmd.com/read/30753611/phase-i-ii-trial-testing-safety-and-immunogenicity-of-the-multipeptide-ima950-poly-iclc-vaccine-in-newly-diagnosed-adult-malignant-astrocytoma-patients
#1
Denis Migliorini, Valérie Dutoit, Mathilde Allard, Nicole Grandjean Hallez, Eliana Marinari, Valérie Widmer, Géraldine Philippin, Francesca Corlazzoli, Robin Gustave, Mario Kreutzfeldt, Nathalie Blazek, Joëlle Wasem, Andreas Hottinger, Avinash Koka, Shahan Momjian, Alexander Lobrinus, Doron Merkler, Maria-Isabel Vargas, Paul R Walker, Anna Patrikidou, Pierre-Yves Dietrich
Background: Peptide vaccines offer the opportunity to elicit glioma-specific T cells with tumor killing ability. Using antigens eluted from the surface of glioblastoma samples, we designed a phase I/II study to test safety and immunogenicity of the IMA950 multipeptide vaccine adjuvanted with poly-ICLC in HLA-A2 + glioma patients. Methods: Adult patients with newly diagnosed glioblastoma (n=16) and grade III astrocytoma (n=3) were treated with radiochemotherapy followed by IMA950/poly-ICLC vaccination...
February 12, 2019: Neuro-oncology
https://read.qxmd.com/read/30719212/photo-immune-therapy-with-liposomally-formulated-phospholipid-conjugated-indocyanine-green-induces-specific-antitumor-responses-with-heat-shock-protein-70-expression-in-a-glioblastoma-model
#2
Sayaka Shibata, Natsuki Shinozaki, Akiko Suganami, Shiro Ikegami, Yuki Kinoshita, Ryozo Hasegawa, Hirata Kentaro, Yoshiharu Okamoto, Ichio Aoki, Yutaka Tamura, Yasuo Iwadate
Glioblastoma (GBM) is the most common malignant brain tumor, and infiltrates into the surrounding normal brain tissue. Induction of a tumor-specific immune response is one of the best methods to obtain tumor-specific cytotoxicity. Photodynamic therapy (PDT) is known to effectively induce an antitumor immune response. We have developed a clinically translatable nanoparticle, liposomally formulated phospholipid-conjugated indocyanine green (LP-iDOPE), applicable for PDT. This nanoparticle accumulates in tumor tissues by the enhanced permeability and retention effect, and releases heat and singlet oxygen to injure cancer cells when activated by near infrared (NIR) light...
January 4, 2019: Oncotarget
https://read.qxmd.com/read/30690106/silica-cloaking-of-adenovirus-enhances-gene-delivery-while-reducing-immunogenicity
#3
Ajay A Sapre, Gen Yong, Ya-San Yeh, Laura E Ruff, Justin S Plaut, Zeynep Sayar, Anupriya Agarwal, Jacqueline Martinez, Theresa N Nguyen, Yu-Tsueng Liu, Bradley T Messmer, Sadik C Esener, Jared M Fischer
Viral gene therapy is a means of delivering genes to replace malfunctioning ones, to kill cancer cells, or to correct genetic mutations. This technology is emerging as a powerful clinical tool; however, it is still limited by viral tropism, uptake and clearance by the liver, and most importantly an immune response. To overcome these challenges, we sought to merge the robustness of viral gene expression and the versatility of nanoparticle technology. Here, we describe a method for cloaking adenovirus (Ad) in silica (SiAd) as a nanoparticle formulation that significantly enhances transduction...
January 25, 2019: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://read.qxmd.com/read/30682795/treatment-combining-cd200-immune-checkpoint-inhibitor-and-tumor-lysate-vaccination-after-surgery-for-pet-dogs-with-high-grade-glioma
#4
Michael R Olin, Elisabet Ampudia-Mesias, Christopher A Pennell, Aaron Sarver, Clark C Chen, Christopher L Moertel, Matthew A Hunt, G Elizabeth Pluhar
Recent advances in immunotherapy have included inhibition of immune checkpoint proteins in the tumor microenvironment and tumor lysate-based vaccination strategies. We combined these approaches in pet dogs with high-grade glioma. Administration of a synthetic peptide targeting the immune checkpoint protein, CD200, enhanced the capacity of antigen-presenting cells to prime T-cells to mediate an anti-glioma response. We found that in canine spontaneous gliomas, local injection of a canine-specific, CD200-directed peptide before subcutaneous delivery of an autologous tumor lysate vaccine prolonged survival relative to a historical control treated with autologous tumor lysate alone (median survivals of 12...
January 24, 2019: Cancers
https://read.qxmd.com/read/30678307/thioridazine-enhances-p62-mediated-autophagy-and-apoptosis-through-wnt-%C3%AE-catenin-signaling-pathway-in-glioma-cells
#5
Cheng-Wei Chu, Huey-Jiun Ko, Chia-Hua Chou, Tai-Shan Cheng, Hui-Wen Cheng, Yu-Hsin Liang, Yun-Ling Lai, Chen-Yen Lin, Chihuei Wang, Joon-Khim Loh, Jiin-Tsuey Cheng, Shean-Jaw Chiou, Chun-Li Su, Chi-Ying F Huang, Yi-Ren Hong
Thioridazine (THD) is a common phenothiazine antipsychotic drug reported to suppress growth in several types of cancer cells. We previously showed that THD acts as an antiglioblastoma and anticancer stem-like cell agent. However, the signaling pathway underlying autophagy and apoptosis induction remains unclear. THD treatment significantly induced autophagy with upregulated AMPK activity and engendered cell death with increased sub-G1 in glioblastoma multiform (GBM) cell lines. Notably, through whole gene expression screening with THD treatment, frizzled (Fzd) proteins, a family of G-protein-coupled receptors, were found, suggesting the participation of Wnt/β-catenin signaling...
January 22, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30677574/immunotherapy-for-high-grade-gliomas-a-clinical-update-and-practical-considerations-for-neurosurgeons
#6
REVIEW
Jacob S Young, Fara Dayani, Ramin A Morshed, Hideho Okada, Manish K Aghi
The current standard of care for patients with high grade gliomas includes surgical resection, chemotherapy, and radiation; but even still the majority of patients experience disease progression and succumb to their illness within a few years of diagnosis. Immunotherapy, which stimulates an anti-tumor immune response, has been revolutionary in the treatment of some hematological and solid malignancies, generating substantial excitement for its potential for patients with glioblastoma. The most commonly used immunotherapies include dendritic cell and peptide vaccines, checkpoint inhibitors, and adoptive T cell therapy...
January 21, 2019: World Neurosurgery
https://read.qxmd.com/read/30668768/modulation-of-temozolomide-dose-differentially-affects-t-cell-response-to-immune-checkpoint-inhibition
#7
Aida Karachi, Changlin Yang, Farhad Dastmalchi, Elias Sayour, Jianping Huang, Hassan Azari, Yu Long, Catherine Flores, Duane A Mitchell, Maryam Rahman
Background: The changes induced in host immunity and the tumor microenvironment by chemotherapy have been shown to impact immunotherapy response in both a positive and negative fashion. Temozolomide is the most common chemotherapy used to treat glioblastoma (GBM) and has been shown to have variable effects on immune response to immunotherapy. Therefore, we aimed to determine the immune modulatory effects of temozolomide that would impact response to immune checkpoint inhibition in the treatment of experimental GBM...
January 22, 2019: Neuro-oncology
https://read.qxmd.com/read/30659522/5-aminolevulinic-acid-photodynamic-therapy-for-the-treatment-of-high-grade-gliomas
#8
REVIEW
K Mahmoudi, K L Garvey, A Bouras, G Cramer, H Stepp, J G Jesu Raj, D Bozec, T M Busch, C G Hadjipanayis
INTRODUCTION: Photodynamic therapy (PDT) is a two-step treatment involving the administration of a photosensitive agent followed by its activation at a specific light wavelength for targeting of tumor cells. MATERIALS/METHODS: A comprehensive review of the literature was performed to analyze the indications for PDT, mechanisms of action, use of different photosensitizers, the immunomodulatory effects of PDT, and both preclinical and clinical studies for use in high-grade gliomas (HGGs)...
January 18, 2019: Journal of Neuro-oncology
https://read.qxmd.com/read/30657567/influences-of-lncrna-snhg20-on-proliferation-and-apoptosis-of-glioma-cells-through-regulating-the-pten-pi3k-akt-signaling-pathway
#9
L-P Guo, Z-J Zhang, R-T Li, H-Y Li, Y-Q Cui
OBJECTIVE:   To investigate the influences of long non-coding ribonucleic acid (lncRNA) small nucleolar RNA host gene 20 (SNHG20) on proliferation and apoptosis of glioma cells, and further explore the mechanism of SNHG20 in the incidence and development of glioma. PATIENTS AND METHODS: A total of 80 cases of glioma specimens and 80 cases of para-carcinoma specimens were collected, and the expression level of SNHG20 was detected via reverse transcription-polymerase chain reaction (RT-PCR)...
January 2019: European Review for Medical and Pharmacological Sciences
https://read.qxmd.com/read/30644426/genetically-distinct-glioma-stem-like-cell-xenografts-established-from-paired-glioblastoma-samples-harvested-before-and-after-molecularly-targeted-therapy
#10
Shota Tanaka, Samantha Luk, Juri Kiyokawa, Maristela L Onozato, A John Iafrate, Khalid Shah, Robert L Martuza, Samuel D Rabkin, Tracy T Batchelor, Daniel P Cahill, Andrew S Chi, Hiroaki Wakimoto
Intratumoural heterogeneity underlies tumour escape from molecularly targeted therapy in glioblastoma. A cell-based model preserving the evolving molecular profiles of a tumour during treatment is key to understanding the recurrence mechanisms and development of strategies to overcome resistance. In this study, we established a matched pair of glioblastoma stem-like cell (GSC) cultures from patient glioblastoma samples before and after epidermal growth factor receptor (EGFR)-targeted therapy. A patient with recurrent glioblastoma (MGG70R) harboring focal, high-level EGFR amplification received the irreversible EGFR tyrosine kinase inhibitor dacomitinib...
January 15, 2019: Scientific Reports
https://read.qxmd.com/read/30632816/novel-immunotherapeutics-for-treatment-of-glioblastoma-the-last-decade-of-research
#11
Emaad Khansur, Ashish H Shah, Kyle Lacy, 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 11, 2019: Cancer Investigation
https://read.qxmd.com/read/30621721/mov10-binding-circ-dicer1-regulates-the-angiogenesis-of-glioma-via-mir-103a-3p-mir-382-5p-mediated-zic4-expression-change
#12
Qianru He, Lini Zhao, Xiaobai Liu, Jian Zheng, Yunhui Liu, Libo Liu, Jun Ma, Heng Cai, Zhen Li, Yixue Xue
BACKGROUND: RNA binding proteins (RBPs) have been reported to interact with RNAs to regulate gene expression. Circular RNAs (circRNAs) are a type of endogenous non-coding RNAs, which involved in the angiogenesis of tumor. The purpose of this study is to elucidate the potential roles and molecular mechanisms of MOV10 and circ-DICER1 in regulating the angiogenesis of glioma-exposed endothelial cells (GECs). METHODS: The expressions of circ-DICER1, miR-103a-3p and miR-382-5p were detected by real-time PCR...
January 8, 2019: Journal of Experimental & Clinical Cancer Research: CR
https://read.qxmd.com/read/30616755/glioblastoma-therapy-in-the-age-of-molecular-medicine
#13
REVIEW
Luiz Henrique Medeiros Geraldo, Celina Garcia, Anna Carolina Carvalho da Fonseca, Luiz Gustavo Feijó Dubois, Tânia Cristina Leite de Sampaio E Spohr, Diana Matias, Eduardo Sabino de Camargo Magalhães, Rackele Ferreira do Amaral, Barbara Gomes da Rosa, Izabella Grimaldi, Felipe Sceanu Leser, José Marcos Janeiro, Lucy Macharia, Caroline Wanjiru, Claudia Maria Pereira, Vivaldo Moura-Neto, Catarina Freitas, Flavia Regina Souza Lima
Glioblastoma (GBM) is the most common and fatal primary malignant brain tumor. Despite advances in the understanding of the biology of gliomas, little has changed in the treatment of these tumors in the past decade. Phase III clinical trials showed no benefit for the use of bevacizumab in newly diagnosed patients, leading to a renewed search for new antiangiogenic drugs, as well as immunotherapeutic approaches, including checkpoint inhibitors, chimeric antigen receptor T cells, and intracerebral CpG-oligodeoxynucleotides...
January 2019: Trends in Cancer
https://read.qxmd.com/read/30584325/expression-of-activating-transcription-factor-5-atf5-is-increased-in-astrocytomas-of-different-who-grades-and-correlates-with-survival-of-glioblastoma-patients
#14
Jonas Feldheim, Almuth F Kessler, Dominik Schmitt, Lara Wilczek, Thomas Linsenmann, Mathias Dahlmann, Camelia M Monoranu, Ralf-Ingo Ernestus, Carsten Hagemann, Mario Löhr
Background: ATF5 suppresses differentiation of neuroprogenitor cells and is overexpressed in glioblastoma (GBM). A reduction of its expression leads to apoptotic GBM cell death. Data on ATF5 expression in astrocytoma WHO grade II (low-grade astrocytoma [LGA]) are scarce and lacking on recurrent GBM. Patients and methods: ATF5 mRNA was extracted from frozen samples of patients' GBM (n=79), LGA (n=40), and normal brain (NB, n=10), quantified by duplex qPCR and correlated with retrospectively collected clinical data...
2018: OncoTargets and Therapy
https://read.qxmd.com/read/30572904/identification-of-a-novel-role-of-il-13r%C3%AE-2-in-human-glioblastoma-multiforme-interleukin-13-mediates-signal-transduction-through-ap-1-pathway
#15
Rukmini Bhardwaj, Akiko Suzuki, Pamela Leland, Bharat H Joshi, Raj K Puri
BACKGROUND: Previously, we have demonstrated that Interleukin 13 receptor alpha 2 (IL-13Rα2) is overexpressed in approximate 78% Glioblastoma multiforme (GBM) samples. We have also demonstrated that IL-13Rα2 can serve as a target for cancer immunotherapy in several pre-clinical and clinical studies. However, the significance of overexpression of IL-13Rα2 in GBM and astrocytoma and signaling through these receptors is not known. IL-13 can signal through IL-13R via JAK/STAT and AP-1 pathways in certain cell lines including some tumor cell lines...
December 20, 2018: Journal of Translational Medicine
https://read.qxmd.com/read/30568502/specific-clinical-and-immune-features-of-cd68-in-glioma-via-1-024-samples
#16
Le Wang, Chaoqi Zhang, Zhen Zhang, Bing Han, Zhibo Shen, Lifeng Li, Shasha Liu, Xuan Zhao, Fanglei Ye, Yi Zhang
Background: There is a growing recognition that tumor-associated macrophages (TAMs) are recruited to the glioma environment, facilitating tumor proliferation and migration by creating an immunosuppressive microenvironment. CD68 has been widely reported as a specific marker of TAMs in cancer. Purpose: To clarify the role of CD68 in glioma, we investigated its function at the transcriptome level and relationship with clinical practice. Patients and methods: In total, 325 RNA-seq data from Chinese Glioma Genome Atlas (CGGA) and 697 RNA-seq data from The Cancer Genome Atlas (TCGA) network were enrolled in this study...
2018: Cancer Management and Research
https://read.qxmd.com/read/30568303/actively-personalized-vaccination-trial-for-newly-diagnosed-glioblastoma
#17
Norbert Hilf, Sabrina Kuttruff-Coqui, Katrin Frenzel, Valesca Bukur, Stefan Stevanović, Cécile Gouttefangeas, Michael Platten, Ghazaleh Tabatabai, Valerie Dutoit, Sjoerd H van der Burg, Per Thor Straten, Francisco Martínez-Ricarte, Berta Ponsati, Hideho Okada, Ulrik Lassen, Arie Admon, Christian H Ottensmeier, Alexander Ulges, Sebastian Kreiter, Andreas von Deimling, Marco Skardelly, Denis Migliorini, Judith R Kroep, Manja Idorn, Jordi Rodon, Jordi Piró, Hans S Poulsen, Bracha Shraibman, Katy McCann, Regina Mendrzyk, Martin Löwer, Monika Stieglbauer, Cedrik M Britten, David Capper, Marij J P Welters, Juan Sahuquillo, Katharina Kiesel, Evelyna Derhovanessian, Elisa Rusch, Lukas Bunse, Colette Song, Sandra Heesch, Claudia Wagner, Alexandra Kemmer-Brück, Jörg Ludwig, John C Castle, Oliver Schoor, Arbel D Tadmor, Edward Green, Jens Fritsche, Miriam Meyer, Nina Pawlowski, Sonja Dorner, Franziska Hoffgaard, Bernhard Rössler, Dominik Maurer, Toni Weinschenk, Carsten Reinhardt, Christoph Huber, Hans-Georg Rammensee, Harpreet Singh-Jasuja, Ugur Sahin, Pierre-Yves Dietrich, Wolfgang Wick
Patients with glioblastoma currently do not sufficiently benefit from recent breakthroughs in cancer treatment that use checkpoint inhibitors1,2 . For treatments using checkpoint inhibitors to be successful, a high mutational load and responses to neoepitopes are thought to be essential3 . There is limited intratumoural infiltration of immune cells4 in glioblastoma and these tumours contain only 30-50 non-synonymous mutations5 . Exploitation of the full repertoire of tumour antigens-that is, both unmutated antigens and neoepitopes-may offer more effective immunotherapies, especially for tumours with a low mutational load...
December 19, 2018: Nature
https://read.qxmd.com/read/30565681/shrna-mediated-ppar%C3%AE-knockdown-in-human-glioma-stem-cells-reduces-in-vitro-proliferation-and-inhibits-orthotopic-xenograft-tumour-growth
#18
H R Haynes, H L Scott, C L Killick-Cole, G Shaw, T Brend, K M Hares, J Redondo, K C Kemp, L S Ballesteros, A Herman, O Cordero-Llana, W G Singleton, F Mills, T Batstone, H Bulstrode, R A Kauppinen, H Wurdak, J B Uney, S C Short, A Wilkins, K M Kurian
The overall survival for patients with primary glioblastoma is very poor. Glioblastoma contains a subpopulation of glioma stem cells (GSC) which are responsible for tumour initiation, treatment resistance and recurrence. PPARα is a transcription factor involved in control of lipid, carbohydrate and amino acid metabolism. We have recently shown that PPARα gene and protein expression is increased in glioblastoma and has independent clinical prognostic significance in multivariate analyses. In this work we report that PPARα is overexpressed in GSC compared to foetal neural stem cells...
November 22, 2018: Journal of Pathology
https://read.qxmd.com/read/30565657/an-effective-dendritic-cell-based-vaccine-containing-glioma-stem-like-cell-lysate-and-cpg-adjuvant-for-an-orthotopic-mouse-model-of-glioma
#19
Shan Zhu, Xinping Lv, Xuhao Zhang, Tete Li, Guoxia Zang, Ning Yang, Xue Wang, Jing Wu, Wei Chen, Yong-Jun Liu, Jingtao Chen
Owing to the limited therapeutic efficacy of glioma vaccines, new strategies are required to improve cancer vaccines. This study aimed to assess the therapeutic efficacy of a glioma vaccine called STDENVANT. This vaccine, comprising glioma stem-like cell (GSC) lysate, dendritic cells (DCs), and Toll-like receptor (TLR) 9 agonist CpG motif-containing oligodeoxynucleotides (CpG ODNs), was assessed using a GL261-C57BL/6 orthotopic mouse model of glioma. STDENVANT markedly improved survival and tumor regression by enhancing anti-tumor immune function...
November 22, 2018: International Journal of Cancer. Journal International du Cancer
https://read.qxmd.com/read/30564636/deep-sequencing-of-circulating-exosomal-microrna-allows-non-invasive-glioblastoma-diagnosis
#20
Saeideh Ebrahimkhani, Fatemeh Vafaee, Susannah Hallal, Heng Wei, Maggie Yuk T Lee, Paul E Young, Laveniya Satgunaseelan, Heidi Beadnall, Michael H Barnett, Brindha Shivalingam, Catherine M Suter, Michael E Buckland, Kimberley L Kaufman
Exosomes are nano-sized extracellular vesicles released by many cells that contain molecules characteristic of their cell of origin, including microRNA. Exosomes released by glioblastoma cross the blood-brain barrier into the peripheral circulation and carry molecular cargo distinct to that of "free-circulating" miRNA. In this pilot study, serum exosomal microRNAs were isolated from glioblastoma ( n  = 12) patients and analyzed using unbiased deep sequencing. Results were compared to sera from age- and gender-matched healthy controls and to grade II-III ( n  = 10) glioma patients...
2018: NPJ Precision Oncology
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