Available online 26 April 2022, 108193

Malignant brain tumors constitute nearly one-third of cancer diagnoses in children and have recently surpassed hematologic malignancies as the most lethal neoplasm in the pediatric population. Outcomes for children with brain tumors are unacceptably poor and current standards of care—surgical resection, chemotherapy, and radiation—are associated with significant long-term morbidity. Oncolytic virotherapy has emerged as a promising immunotherapy for the treatment of brain tumors. While the majority of brain tumor clinical trials utilizing oncolytic virotherapy have been in adults, five viruses are being tested in pediatric brain tumor clinical trials: herpes simplex virus (G207), reovirus (pelareorep/Reolysin), measles virus (MV-NIS), poliovirus (PVSRIPO), and adenovirus (DNX-2401, AloCELYVIR). Herein, we review past and current pediatric immunovirotherapy brain tumor trials including the relevant preclinical and clinical research that contributed to their development. We describe mechanisms by which the viruses may overcome barriers in treating pediatric brain tumors, examine challenges associated with achieving effective, durable responses, highlight unique aspects and successes of the trials, and discuss future directions of immunovirotherapy research for the treatment of pediatric brain tumors.

Pediatric

Oncolytic

Virotherapy

Immunotherapy

Brain tumors

Glioma

allogenic mesenchymal stem cells loaded with ICOVIR-5

atypical teratoid/rhabdoid tumor

carcinoembryonic antigen

convection-enhanced delivery

autologous bone marrow-derived mesenchymal stem cells loaded with ICOVIR-5

central nervous system

diffuse intrinsic pontine glioma

granulocyte-macrophage colony-stimulating factor

Herpes Simplex Virus-1

isocitrate dehydrogenase

internal ribosomal entry site

maximum tolerated dose

engineered oncolytic measles virus expressing carcinoembryonic antigen

engineered oncolytic measles virus expressing sodium iodide symporter

sodium iodide symporter

engineered oncolytic HSV-1

primitive neuroectodermal tumors

PV (Sabin)-Rhinovirus IRES PV Open reading frame

arginine-glycine-aspartate

Recommended Phase 2 Dose

talimogene laherparepvec

median tissue culture infectious dose

tumor mutational burden.

© 2022 Published by Elsevier Inc.