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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...


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T lymphocyte-targeted immune checkpoint modulation in glioma

Immunomodulatory therapies targeting inhibitory checkpoint molecules have revolutionized the treatment of solid tumor malignancies. Concerns about whether systemic administration of an immune checkpoint inhibitor could impact primary brain tumors were answered with the observation of definitive...


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Combined innate and adaptive immunotherapy overcomes resistance of immunologically cold syngeneic murine neuroblastoma to checkpoint inhibition

Unlike some adult cancers, most pediatric cancers are considered immunologically cold and generally less responsive to immunotherapy. While immunotherapy has already been incorporated into standard of care treatment for pediatric patients with high-risk neuroblastoma, overall survival remains...


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CRISPR-Cas9 disruption of PD-1 enhances activity of universal EGFRvIII CAR T cells in a preclinical model of human glioblastoma

Despite remarkable success in the treatment of hematological malignancies, CAR T-cell therapies for solid tumors have floundered, in large part due to local immune suppression and the effects of prolonged stimulation leading to T-cell dysfunction and exhaustion. One mechanism by which gliomas...



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Diverse immunotherapies can effectively treat syngeneic brainstem tumors in the absence of overt toxicity

Immunotherapy has shown remarkable clinical promise in the treatment of various types of cancers. However, clinical benefits derive from a highly inflammatory mechanism of action. This presents unique challenges for use in pediatric brainstem tumors including diffuse intrinsic pontine glioma ...


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T cells expressing NKG2D chimeric antigen receptors efficiently eliminate glioblastoma and cancer stem cells

Traditional therapies fail to cure most glioblastoma patients and the 5-year survival rate is less than 10%, highlighting need for new therapeutic approaches. The natural killer group 2 member D ligands (NKG2DLs) are highly expressed in glioblastomas and are considered promising targets for...