[en] Oncolytic viral-based therapies are gaining increasing attention as a promising therapeutic approach for high-grade gliomas. Converging evidence suggests the possibility of an anti-tumoral immune response that is responsible for tumor eradication, leaving room for immune activation as a synergistic treatment option2–5. In this issue, Rivera-Molina et al. report on the utility of the clinical-trial tested oncolytic Delta-24-RGD virus that is engineered to be armed with a positive activator of the tumor necrosis factor receptor superfamily synapsis: GITRL/GITR1. The authors demonstrate increased recruitment and activation of T-cells in tumors of mice treated with the armed oncolytic antivirus, dubbed Delta-24-GREAT, with associated improved survival in-vivo in comparison to mice treated with Delta-24-RGD alone. Histopathological examination demonstrated extensive necrosis within Delta-24-GREAT treated tissue. The results of this study highlight an opportunity to overcome the intrinsic lack of co-stimulatory molecules in cancer cells to trigger robust immune responses in high-grade gliomas. The complement of available T-cell activators may be exploited in future studies to achieve synergistic anti-neoplastic effects in glioblastoma with hopes of rapid translation of armed viruses into controlled clinical trials.
Disciplines :
Oncology
Author, co-author :
Nassiri, Farshad; Division of Neurosurgery, University Health Network and MacFeeters-Hamilton Neuro-Oncology Program, Princess Margaret Hospital, University of Toronto, Toronto, Canada.
Aldape, Kenneth; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
Alhuwalia, Manmeet; Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center and Department of Hematology/Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.
Brastianos, Priscilla; Divisions of Hematology/Oncology and Neuro-Oncology, Departments of Medicine and Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts.
Ducray, Francois; Department of Neuro-Oncology, Hospices Civils de Lyon, Lyon, France.
Galldiks, Norbert; Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne and Germany Institute of Neuroscience and Medicine (INM-3), Research Center Juelich, Juelich and Germany Center of Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne, and Duesseldorf, Germany.
Kim, Albert; Department of Neurosurgery, School of Medicine, Washington University, St. Louis, Missouri.
Lamszus, Katrin; Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Mitchell, Duane; Lillian S. Wells Department of Neurosurgery, UF Brain Tumor Immunotherapy Program, Preston A. Wells, Jr. Center for Brain Tumor Therapy, University of Florida, Gainesville, Florida.
Nabors, L Burt; Department of Neurology, University of Alabama, Birmingham, Birmingham, Alabama.
Nam, Do-Hyun; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea.
Natsume, Atsushi; Department of Neurosurgery, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Ng, Ho-Keung; Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China.
NICLOU, Simone P. ; University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) ; Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany.
Sahm, Felix; NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg, Luxembourg.
Short, Susan; Leeds Institute of Cancer and Pathology, Faculty of Medicine and Health, University of Leeds, St James's University Hospital, Leeds, West Yorkshire.
Walsh, Kyle; Duke Cancer Institute, Duke University, Durham, North Carolina.
Wick, Wolfgang; University Medical Center and German Cancer Research Center Heidelberg, Germany.
Zadeh, Gelareh; Division of Neurosurgery, University Health Network and MacFeeters-Hamilton Neuro-Oncology Program, Princess Margaret Hospital, University of Toronto, Toronto, Canada.
Rivera-Molina Y, Jiang H, Fueyo J, et al. GITRL-armed Delta-24-RGD oncolytic adenovirus prolongs survival and induces anti-glioma immune memory. Neuro-Oncology Adv. 2019;1(1). doi:10.1093/noajnl/vdz009.
Chiocca EA, Abbed KM, Tatter S, et al. A Phase I Open-Label, Dose-Escalation, Multi-Institutional Trial of Injection with an E1B-Attenuated Adenovirus, ONYX-015, into the Peritumoral Region of Recurrent Malignant Gliomas, in the Adjuvant Setting. Mol Ther. 2004;10(5):958-966. doi:10.1016/j.ymthe.2004.07.021.
Desjardins A, Gromeier M, Herndon JE, et al. Recurrent Glioblastoma Treated with Recombinant Poliovirus. N Engl J Med. 2018;379(2):150-161. doi:10.1056/NEJMoa1716435.
Chiocca EA, Nassiri F, Wang J, Peruzzi P, Zadeh G. Viral and other therapies for recurrent glioblastoma: is a 24-month durable response unusual? Neuro Oncol. 2019;21(1):14-25. doi:10.1093/neuonc/noy170.
Lang FF, Conrad C, Gomez-Manzano C, et al. Phase I Study of DNX-2401 (Delta-24-RGD) Oncolytic Adenovirus: Replication and Immunotherapeutic Effects in Recurrent Malignant Glioma. J Clin Oncol. 2018;36(14):1419-1427. doi:10.1200/JCO.2017.75.8219.
Wijnenga MMJ, van der Voort SR, French PJ, et al. Differences in spatial distribution between WHO 2016 low-grade glioma molecular subgroups. Neuro-Oncology Adv. 2019;1(1). doi:10.1093/noajnl/ vdz001.
Lai A, Kharbanda S, Pope WB, et al. Evidence for sequenced molecular evolution of IDH1 mutant glioblastoma from a distinct cell of origin. J Clin Oncol. 2011;29(34):4482-4490. doi:10.1200/JCO.2010.33.8715.
Tejada Neyra MA, Neuberger U, Reinhardt A, et al. Voxel-wise radiogenomic mapping of tumor location with key molecular alterations in patients with glioma. Neuro Oncol. 2018;20(11):1517-1524. doi:10.1093/neuonc/noy134.
Livermore LJ, Isabelle M, Bell IM, et al. Rapid intraoperative molecular genetic classification of gliomas using Raman spectroscopy. Neuro-Oncology Adv. 2019;1(1). doi:10.1093/noajnl/vdz008.
Longuespée R, Wefers AK, De Vita E, et al. Rapid detection of 2-hydroxyglutarate in frozen sections of IDH mutant tumors by MALDITOF mass spectrometry. Acta Neuropathol Commun. 2018;6(1):21. doi:10.1186/s40478-018-0523-3.
Sim H-W, Nejad R, Zhang W, et al. Tissue 2-Hydroxyglutarate as a Biomarker for Isocitrate Dehydrogenase Mutations in Gliomas. Clin Cancer Res. 2019;25(11):3366-3373. doi:10.1158/1078-0432.CCR-18-3205.
Munegowda MA, Fisher C, Molehuis D, et al. Efficacy of Ruthenium coordination complex based Rutherrin in a pre-clinical rat glioblastoma(GBM) model. Neuro-Oncology Adv. May 2019. doi:10.1093/noajnl/vdz006.
Gittleman H, Cioffi G, Chunduru P, et al. An independently validated nomogram for IDH-wildtype glioblastoma patient survival. Neuro-Oncology Adv. 2019;1(1). doi:10.1093/noajnl/vdz007.
Aibaidula A, Chan AK-Y, Shi Z, et al. Adult IDH wild-type lower-grade gliomas should be further stratified. Neuro Oncol. 2017;19(10):1327-1337. doi:10.1093/neuonc/nox078.
Gittleman H, Lim D, Kattan MW, et al. An independently validated nomogram for individualized estimation of survival among patients with newly diagnosed glioblastoma: NRG Oncology RTOG 0525 and 0825. Neuro Oncol. 2017;19(5):669-677. doi:10.1093/neuonc/now208.
Chang R, Tosi U, Voronina J, et al. Combined Targeting of PI3K and MEK Effector Pathways via CED for DIPG Therapy. Neuro-Oncology Adv. 2019;1(1). doi:10.1093/noajnl/vdz004.
Pollack IF, Stewart CF, Kocak M, et al. A phase II study of gefitinib and irradiation in children with newly diagnosed brainstem gliomas: A report from the Pediatric Brain Tumor Consortium. Neuro Oncol. 2011;13(3):290-297. doi:10.1093/neuonc/noq199.
Souweidane MM, Kramer K, Pandit-Taskar N, et al. Convectionenhanced delivery for diffuse intrinsic pontine glioma: a single-centre, dose-escalation, phase 1 trial. Lancet Oncol. 2018;19(8):1040-1050. doi:10.1016/S1470-2045(18)30322-X.
Portet S, Naoufal R, Tachon G, et al. Histo-molecular characterization of intracranial meningiomas developed in patients exposed to high-dose cyproterone acetate: an antiandrogen treatment. Neuro-Oncology Adv. 2019;1(1). doi:10.1093/noajnl/vdz003.
Gil M, Oliva B, Timoner J, Maciá MA, Bryant V, de Abajo FJ. Risk of meningioma among users of high doses of cyproterone acetate as compared with the general population: evidence from a populationbased cohort study. Br J Clin Pharmacol. 2011;72(6):965-968. doi:10.1111/j.1365-2125.2011.04031.x.
Brastianos PK, Horowitz PM, Santagata S, et al. Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations. Nat Genet. 2013;45(3):285-289. doi:10.1038/ng.2526.
Clark VE, Erson-Omay EZ, Serin A, et al. Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO. Science. 2013;339(6123):1077-1080. doi:10.1126/science.1233009.
Abedalthagafi M, Bi WL, Aizer AA, et al. Oncogenic PI3K mutations are as common as AKT1 and SMO mutations in meningioma. Neuro Oncol. 2016;18(5):649-655. doi:10.1093/neuonc/nov316.
Peyre M, Gaillard S, de Marcellus C, et al. Progestin-associated shift of meningioma mutational landscape. Ann Oncol Off J Eur Soc Med Oncol. 2018;29(3):681-686. doi:10.1093/annonc/mdx763.
Agnihotri S, Suppiah S, Tonge PD, et al. Therapeutic radiation for childhood cancer drives structural aberrations of NF2 in meningiomas. Nat Commun. 2017;8(1):186. doi:10.1038/s41467-017-00174-7.
Sahm F, Toprak UH, Hübschmann D, et al. Meningiomas induced by low-dose radiation carry structural variants of NF2 and a distinct mutational signature. Acta Neuropathol. 2017;134(1):155-158. doi:10.1007/s00401-017-1715-9.
Morin O, Chen WC, Nassiri F, et al. Integrated models incorporating radiologic and radiomic features predict meningioma grade, local failure and overall survival. Neuro-Oncology Adv. 2019;1(1). doi:10.1093/noajnl/vdz011.
Galldiks N, Lohmann P, Albert NL, Tonn JC, Langen K-J. Current Status of PET Imaging in Neuro-Oncology. Neuro-Oncology Adv. 2019;1(1). doi:10.1093/noajnl/vdz010.
Albert NL, Weller M, Suchorska B, et al. Response Assessment in Neuro-Oncology working group and European Association for Neuro-Oncology recommendations for the clinical use of PET imaging in gliomas. Neuro Oncol. 2016;18(9):1199-1208. doi:10.1093/neuonc/now058.
Langen K-J, Watts C. Amino acid PET for brain tumours-ready for the clinic? Nat Rev Neurol. 2016;12(7):375-376. doi:10.1038/ nrneurol.2016.80.
Sambade MJ, Van Swearingen AED, McClure MB, et al. Efficacy and pharmacodynamics of niraparib in BRCA-mutant and wildtype intracranial triple negative breast cancer murine models. Neuro-Oncology Adv. 2019;1(1). doi:10.1093/noajnl/vdz005.
Diossy M, Reiniger L, Sztupinszki Z, et al. Breast cancer brain metastases show increased levels of genomic aberration-based homologous recombination deficiency scores relative to their corresponding primary tumors. Ann Oncol. 2018;29(9):1948-1954. doi:10.1093/annonc/mdy216.
