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Open AccessClinical trial links oncolytic immunoactivation to survival in glioblastoma
Immunotherapy failures can result from the highly suppressive tumour microenvironment that characterizes aggressive forms of cancer such as recurrent glioblastoma (rGBM)1,2. Here we report the results of a first-...
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Article
Specific targeting of glioblastoma with an oncolytic virus expressing a cetuximab-CCL5 fusion protein via innate and adaptive immunity
Chemokines such as C-C motif ligand 5 (CCL5) regulate immune cell trafficking in the tumor microenvironment (TME) and govern tumor development, making them promising targets for cancer therapy. However, short ...
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Article
Variants of the adeno-associated virus serotype 9 with enhanced penetration of the blood–brain barrier in rodents and primates
The development of gene therapies for the treatment of diseases of the central nervous system has been hindered by the limited availability of adeno-associated viruses (AAVs) that efficiently traverse the bloo...
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Treat and repeat: oncolytic virus therapy for brain cancer
A study evaluating serial injections of oncolytic virus therapy shows promising outcomes in patients with glioblastoma, and opens the door to longitudinal study designs with the potential to yield rich molecul...
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Open AccessTarget receptor identification and subsequent treatment of resected brain tumors with encapsulated and engineered allogeneic stem cells
Cellular therapies offer a promising therapeutic strategy for the highly malignant brain tumor, glioblastoma (GBM). However, their clinical translation is limited by the lack of effective target identification...
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Quantitative imaging of apoptosis following oncolytic virotherapy by magnetic resonance fingerprinting aided by deep learning
Non-invasive imaging methods for detecting intratumoural viral spread and host responses to oncolytic virotherapy are either slow, lack specificity or require the use of radioactive or metal-based contrast age...
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Article
Advances in local therapy for glioblastoma — taking the fight to the tumour
Despite advances in neurosurgery, chemotherapy and radiotherapy, glioblastoma remains one of the most treatment-resistant CNS malignancies, and the tumour inevitably recurs. The majority of recurrences appear ...
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Article
Glial and myeloid heterogeneity in the brain tumour microenvironment
Brain cancers carry bleak prognoses, with therapeutic advances hel** only a minority of patients over the past decade. The brain tumour microenvironment (TME) is highly immunosuppressive and differs from tha...
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Article
Open AccessAn oncolytic virus expressing a full-length antibody enhances antitumor innate immune response to glioblastoma
Oncolytic herpes simplex virus-1 is capable of lysing tumor cells while alerting the immune system. CD47, in collaboration with SIRPα, represents an important immune checkpoint to inhibit phagocytosis by innat...
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Article
Open AccessRedesigned reporter gene for improved proton exchange-based molecular MRI contrast
Reporter gene imaging allows for non-invasive monitoring of molecular processes in living cells, providing insights on the mechanisms underlying pathology and therapy. A lysine-rich protein (LRP) chemical exch...
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Open AccessKLF4K409Q–mutated meningiomas show enhanced hypoxia signaling and respond to mTORC1 inhibitor treatment
Meningioma represents the most common primary brain tumor in adults. Recently several non-NF2 mutations in meningioma have been identified and correlated with certain pathological subtypes, locations and clinical...
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Mechanisms and therapeutic implications of hypermutation in gliomas
A high tumour mutational burden (hypermutation) is observed in some gliomas1–5; however, the mechanisms by which hypermutation develops and whether it predicts the response to immunotherapy are poorly understood....
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Open AccessGlioblastoma infiltration of both tumor- and virus-antigen specific cytotoxic T cells correlates with experimental virotherapy responses
The mode of action for oncolytic viruses (OVs) in cancer treatment is thought to depend on a direct initial cytotoxic effect against infected tumor cells and subsequent activation of immune cell responses dire...
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Molecular responses to immune checkpoint blockade in glioblastoma
Transcriptional signatures and immune cell infiltrates associated with immune activation distinguish patients with glioblastoma who initially respond to immune checkpoint blockade from those who do not.
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Article
Open AccessThe functional synergism of microRNA clustering provides therapeutically relevant epigenetic interference in glioblastoma
MicroRNA deregulation is a consistent feature of glioblastoma, yet the biological effect of each single gene is generally modest, and therapeutically negligible. Here we describe a module of microRNAs, constit...
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Correction: Amendments: Publisher Correction: An oncolytic herpesvirus expressing E-cadherin improves survival in mouse models of glioblastoma
Nat. Biotechnol.; 10.1038/nbt.4302; corrected online 19 December 2018 In the HTML and PDF versions of this article initially published online, KLRG1− should have read KLRG1+ in the first instance of the phrase...
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An oncolytic herpesvirus expressing E-cadherin improves survival in mouse models of glioblastoma
An engineered oncolytic herpesvirus shows enhanced intratumoral spread, resistance to NK cell clearance and improved efficacy against brain cancer in mice.
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Local Therapies
Local therapies in the context of cranial tumor encompass the concept of local application or local delivery, respectively. Apart from surgical resection which is the most obvious form of local therapy, radiat...
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Article
Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial
Neoantigens, which are derived from tumour-specific protein-coding mutations, are exempt from central tolerance, can generate robust immune responses1,2 and can function as bona fide antigens that facilitate tumo...
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Viruses in cancer therapy — from benchwarmers to quarterbacks
A recent clinical trial of a virotherapy approach, consisting of an engineered poliovirus, has provided evidence of apparently durable responses in patients with recurrent glioblastoma. The results of this tri...