J Neuropathol Exp Neurol. 2018 Aug 1;77(8):696-702. doi: 10.1093/jnen/nly045.
Poliovirus Receptor (CD155) Expression in Pediatric Brain Tumors Mediates Oncolysis of Medulloblastoma and Pleomorphic Xanthoastrocytoma.
Thompson EM1,2, Brown M1, Dobrikova E1, Ramaswamy V3, Taylor MD4,5, McLendon R6, Sanks J6, Chandramohan V2,6, Bigner D2,6, Gromeier M1,2.
Department of Neurosurgery, Duke University, Durham, North Carolina.
Preston Robert Tisch Brain Tumor Center, Duke University, Durham, North Carolina.
Division of Haematology/Oncology, The Arthur and Sonia Labatt Brain Tumour Research Centre, Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
Division of Neurosurgery, The Arthur and Sonia Labatt Brain Tumour Research Centre, Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Poliovirus oncolytic immunotherapy is a putatively novel approach to treat pediatric brain tumors. This work sought to determine expression of the poliovirus receptor (PVR), CD155, in low-grade and malignant pediatric brain tumors and its ability to infect, propagate, and inhibit cell proliferation. CD155 expression in pleomorphic xanthoastrocytoma (PXA), medulloblastoma, atypical teratoid rhabdoid tumor, primitive neuroectodermal tumor, and anaplastic ependymoma specimens was assessed. The ability of the polio: rhinovirus recombinant, PVSRIPO, to infect PXA (645 [BRAF V600E mutation], 2363) and medulloblastoma (D283, D341) cells were determined by viral propagation measurement and cell proliferation. PVR mRNA expression was evaluated in 763 medulloblastoma and 1231 normal brain samples. CD155 was expressed in all 12 patient specimens and in PXA and medulloblastoma cell lines. One-step growth curves at a multiplicity of infection of 10 demonstrated productive infection and peak plaque formation units at 5-10 hours. PVSRIPO infection significantly decreased cellular proliferation in 2363, 645, and D341 cell lines at 48 hours (p < 0.05) and resulted in cell death. PVR expression was highest in medulloblastoma subtypes Group 3γ, WNTα, and WNTβ (p < 0.001). This proof-of-concept in vitro study demonstrates that PVSRIPO is capable of infecting, propagating, prohibiting cell proliferation, and killing PXA and Group 3 medulloblastoma.