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Subtype and grade-dependent spatial heterogeneity of T-cell infiltration in pediatric glioma

Brain tumors are the leading cause of cancer-related mortality in children and have distinct genomic and molecular features compared with adult glioma. However, the properties of immune cells in these tumors has been vastly understudied compared with their adult counterparts. The authors...


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Biomarkers for immunotherapy for treatment of glioblastoma

There are many clinical trials testing immune therapies in glioblastoma (GBM), but patient responses in these studies have been highly variable and a definitive benefit has yet to be identified. Biomarkers are used to quantify normal physiology and physiological response to therapies. When...


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Temozolomide antagonizes oncolytic immunovirotherapy in glioblastoma

Temozolomide (TMZ) chemotherapy is a current standard of care for glioblastoma (GBM), however it has only extended overall survival by a few months. Because it also modulates the immune system, both beneficially and negatively, understanding how TMZ interacts with immunotherapeutics is important...


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Enhanced B7-H4 expression in gliomas with low PD-L1 expression identifies super-cold tumors

Characterizing expression profiles of different immune checkpoint molecules are promising for personalized checkpoint inhibitory immunotherapy. Gliomas have been shown as potential targets for immune checkpoint inhibitors recently. This study was performed to determine coexpression levels of two...


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Immune involvement of the contralateral hemisphere in a glioblastoma mouse model

Glioblastoma (GBM) is the most common and deadliest form of brain cancer in adults. Standard treatment, consisting of surgery and radiochemotherapy, only provides a modest survival benefit and is incapable of combating infiltrating GBM cells in other parts of the brain. New therapies in clinical...


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First in human dose calculation of a single-chain bispecific antibody targeting glioma using the MABEL approach

First-in-human (FIH) clinical trials require careful selection of a safe yet biologically relevant starting dose. Typically, such starting doses are selected based on toxicity studies in a pharmacologically relevant animal model. However, with the advent of target-specific and highly active...


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Longitudinal NK cell kinetics and cytotoxicity in children with neuroblastoma enrolled in a clinical phase II trial

Natural killer (NK) cells are one of the main effector populations of immunotherapy with monoclonal antibody and cytokines, used in combination with chemotherapy to treat children with high-risk neuroblastoma on this phase II trial. However, the impact of chemoimmunotherapy on NK cell kinetics,...


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Pre-existing antitherapeutic antibodies against the Fc region of the hu14.18K322A mAb are associated with outcome in patients with relapsed neuroblastoma

Patients with cancer receiving tumor-reactive humanized monoclonal antibody (mAb) therapy can develop a human antihuman antibody (HAHA) response against the therapeutic mAb. The authors evaluated for HAHA in patients with neuroblastoma treated in a phase I study of humanized anti-GD2 mAb ...


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Potent STING activation stimulates immunogenic cell death to enhance antitumor immunity in neuroblastoma

Neuroblastoma (NB) is a childhood cancer for which new treatment options are needed. The success of immune checkpoint blockade in the treatment of adult solid tumors has prompted the exploration of immunotherapy in NB; however, clinical evidence indicates that the vast majority of NB patients do...


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Peritumoral administration of IFNβ upregulated mesenchymal stem cells inhibits tumor growth in an orthotopic, immunocompetent rat glioma model

Immunotherapy with IFNβ is a promising strategy for treating malignant glioma. However, systemic administration of IFNβ is inadequate because of low intratumoral concentration and major adverse effects. This study aimed to determine whether mesenchymal stem cells (MSCs) can be used as cellular...