Phase I Trial of DNX-2401 for Diffuse Intrinsic Pontine Glioma Newly Diagnosed in Pediatric Patients

Tejada, Sonia; Alonso, Marta M.; Patiño, Ana; Fueyo, Juan; Gomez-Manzano, Candelaria; Díez-Valle, Ricardo

doi:10.1093/neuros/nyx507

Cited by 43 publications

(38 citation statements)

References 7 publications

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“…The tumor specificity is given by the presence of the cyclic arginine/glycine/aspartic acid (RGD) peptide into the viral capsid region responsible for attachment to host cells; the RGD peptide directs the virus towards RGD-binding integrins, which are highly expressed in gliomas. Preliminary recently published results from trials show that therapy with DNX-2401 in combination with temozolomide or interferon-γ is well tolerated and shows significant therapeutic activity [ 57 , 58 ].…”

Section: New Strategiesmentioning

confidence: 99%

Glioblastoma under Siege: An Overview of Current Therapeutic Strategies

2018

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Glioblastoma is known to be one of the most lethal and untreatable human tumors. Surgery and radiotherapy in combination with classical alkylating agents such as temozolomide offer little hope to escape a poor prognosis. For these reasons, enormous efforts are currently devoted to refine in vivo and in vitro models with the specific goal of finding new molecular aberrant pathways, suitable to be targeted by a variety of therapeutic approaches, including novel pharmaceutical formulations and immunotherapy strategies. In this review, we will first discuss current molecular classification based on genomic and transcriptomic criteria. Also, the state of the art in current clinical practice for glioblastoma therapy in the light of the recent molecular classification, together with ongoing phases II and III clinical trials, will be described. Finally, new pharmaceutical formulations such as nanoparticles and viral vectors, together with new strategies entailing the use of monoclonal antibodies, vaccines and immunotherapy agents, such as checkpoint inhibitors, will also be discussed.

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Section: New Strategiesmentioning

confidence: 99%

Glioblastoma under Siege: An Overview of Current Therapeutic Strategies

2018

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“…A trial investigating oncolytic poliovirus immunotherapy with PVSRIPO, a recombinant polio/rhinovirus, delivered by convection‐enhanced delivery is currently recruiting pediatric patients with recurrent/progressive HGG (NCT03043391). Additionally, the oncolytic adenovirus DNX‐2401 is being evaluated in children with treatment‐naïve DIPG via intratumoral injection following stereotactic tumor biopsy (NCT03178032) . Furthermore, intravenous reovirus (Reolysin) is also being looked at, together with GM‐CSF, in pediatric patients with a range of high‐grade brain tumors, including HGG and DIPG (NCT02444546).…”

Section: Immunotherapeutic and Immunomodulatory Agents In Phggmentioning

confidence: 99%

“…Additionally, the oncolytic adenovirus DNX-2401 is being evaluated in children with treatment-naïve DIPG via intratumoral injection following stereotactic tumor biopsy (NCT03178032). 78,79 Furthermore, intravenous reovirus (Reolysin) is also being looked at, together with GM-CSF, in pediatric patients with a range of high-grade brain tumors, including HGG and DIPG (NCT02444546). Finally, tumor regression has been demonstrated in a small case series of pediatric patients with recurrent HGG following treatment with Newcastle disease virus (MTH-68/H).…”

Section: Oncolytic Virotherapymentioning

confidence: 99%

Challenging the indiscriminate use of temozolomide in pediatric high‐grade gliomas: A review of past, current, and emerging therapies

Guerra‐García

Marshall

Cockle

et al. 2019

Pediatric Blood & Cancer

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Pediatric high‐grade gliomas (pHGG) constitute 8% to 12% of primary brain tumors in childhood. The most widely utilized treatment encompasses surgical resection followed by focal radiotherapy and temozolomide. However, experiences over past decades have not demonstrated improved outcomes. pHGG have been classified into different molecular subgroups defined by mutations in histone 3, IDH gene, MAPK pathway, and others, thereby providing a rationale for various targeted therapies. Additionally, immunotherapy and drug repurposing have also become attractive adjunctive treatments. This review focuses on past, present, and emerging treatments for pHGG integrating molecular research with the mainstream pediatric drug development in Europe and the United States to sketch a way forward in the development of novel therapeutic approaches. The implementation of randomized clinical trials with adaptive designs, underpinned by a robust biological rationale, and harnessing collaboration between the pharmaceutical industry, academia, regulators and patients/parents organizations will be essential to improve the outcomes for these children.

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“…To date, at least five oncolytic viruses have been evaluated clinically in children with brain tumors: recombinant poliovirus [27,28] , adenovirus [29] , reovirus [30] , herpesvirus [31,32] , and new castle disease virus [33,34] .…”

Section: Tvec Enters Tumor Cells Through Nectin Adhesion Molecules Anmentioning

confidence: 99%

Immunotherapy for pediatric brain tumors

Landi¹,

Thompson²,

Ashley³

2018

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Immunotherapy, while effective against lymphoid cancers and some solid tumors, has shown less benefit against pediatric brain tumors. Tumor heterogeneity, a suppressive immune microenvironment, and the blood-brain barrier have the potential to diminish any immune-based approach and limit efficacy. More importantly, most pediatric brain tumors are immunologically quiescent, stemming from a low mutational burden. This review focuses on innate vs. adaptive immunotherapeutic approaches and describes how the immunologic context of pediatric brain tumors can help identify well-suited immunotherapies for our patients. In this framework, we will discuss past and current approaches using virotherapy, immunoconjugates, monoclonal antibodies, active immunization, and adoptive cellular therapy, and share our thoughts on how immunotherapy can cure children with brain tumors.

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Phase I Trial of DNX-2401 for Diffuse Intrinsic Pontine Glioma Newly Diagnosed in Pediatric Patients

Cited by 43 publications

References 7 publications

Glioblastoma under Siege: An Overview of Current Therapeutic Strategies

Glioblastoma under Siege: An Overview of Current Therapeutic Strategies

Challenging the indiscriminate use of temozolomide in pediatric high‐grade gliomas: A review of past, current, and emerging therapies

Immunotherapy for pediatric brain tumors

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