Alexander F Haddad1, Jacob S Young1, Nikhil V Mummaneni1, Noriyuki Kasahara1,2, Manish K Aghi3. 1. Department of Neurological Surgery, University of California, 505 Parnassus Ave, M-779, San Francisco, CA, 94143-0112, USA. 2. Department of Radiation Oncology, University of California, San Francisco, CA, USA. 3. Department of Neurological Surgery, University of California, 505 Parnassus Ave, M-779, San Francisco, CA, 94143-0112, USA. manish.aghi@ucsf.edu.
Abstract
INTRODUCTION: The treatment for glioblastoma (GBM) has remained unchanged for the past decade, with only minimal improvements in patient survival. As a result, novel treatments are needed to combat this devastating disease. Immunotherapies are treatments that stimulate the immune system to attack tumor cells and can be either local or systemically delivered. Viral treatments can lead to direct tumor cell death through their natural lifecycle or through the delivery of a suicide gene, with the potential to generate an anti-tumor immune response, making them interesting candidates for combinatorial treatment with immunotherapy. METHODS: We review the current literature surrounding the interactions between oncolytic viruses and the immune system as well as the use of oncolytic viruses combined with immunotherapies for the treatment of GBM. RESULTS: Viral therapies have exhibited preclinical efficacy as single-agents and are being investigated in that manner in clinical trials. Oncolytic viruses have significant interactions with the immune system, although this can also vary depending on the strain of virus. Combinatorial treatments using both oncolytic viruses and immunotherapies have demonstrated promising preclinical findings. CONCLUSIONS: Studies combining viral and immunotherapeutic treatment modalities have provided exciting results thus far and hold great promise for patients with GBM. Additional studies assessing the clinical efficacy of these treatments as well as improved preclinical modeling systems, safety mechanisms, and the balance between treatment efficacy and immune-mediated viral clearance should be considered.
INTRODUCTION: The treatment for glioblastoma (GBM) has remained unchanged for the past decade, with only minimal improvements in patient survival. As a result, novel treatments are needed to combat this devastating disease. Immunotherapies are treatments that stimulate the immune system to attack tumor cells and can be either local or systemically delivered. Viral treatments can lead to direct tumor cell death through their natural lifecycle or through the delivery of a suicide gene, with the potential to generate an anti-tumor immune response, making them interesting candidates for combinatorial treatment with immunotherapy. METHODS: We review the current literature surrounding the interactions between oncolytic viruses and the immune system as well as the use of oncolytic viruses combined with immunotherapies for the treatment of GBM. RESULTS: Viral therapies have exhibited preclinical efficacy as single-agents and are being investigated in that manner in clinical trials. Oncolytic viruses have significant interactions with the immune system, although this can also vary depending on the strain of virus. Combinatorial treatments using both oncolytic viruses and immunotherapies have demonstrated promising preclinical findings. CONCLUSIONS: Studies combining viral and immunotherapeutic treatment modalities have provided exciting results thus far and hold great promise for patients with GBM. Additional studies assessing the clinical efficacy of these treatments as well as improved preclinical modeling systems, safety mechanisms, and the balance between treatment efficacy and immune-mediated viral clearance should be considered.
Authors: Annick Desjardins; Matthias Gromeier; James E Herndon; Nike Beaubier; Dani P Bolognesi; Allan H Friedman; Henry S Friedman; Frances McSherry; Andrea M Muscat; Smita Nair; Katherine B Peters; Dina Randazzo; John H Sampson; Gordana Vlahovic; William T Harrison; Roger E McLendon; David Ashley; Darell D Bigner Journal: N Engl J Med Date: 2018-06-26 Impact factor: 91.245
Authors: Henry M Smilowitz; Jakob Weissenberger; Joachim Weis; Judith D Brown; Rachel J O'Neill; Jean A Laissue Journal: J Neurosurg Date: 2007-04 Impact factor: 5.115
Authors: S Gagandeep; R Brew; B Green; S E Christmas; D Klatzmann; G J Poston; A R Kinsella Journal: Cancer Gene Ther Date: 1996 Mar-Apr Impact factor: 5.987
Authors: Roger Stupp; Warren P Mason; Martin J van den Bent; Michael Weller; Barbara Fisher; Martin J B Taphoorn; Karl Belanger; Alba A Brandes; Christine Marosi; Ulrich Bogdahn; Jürgen Curschmann; Robert C Janzer; Samuel K Ludwin; Thierry Gorlia; Anouk Allgeier; Denis Lacombe; J Gregory Cairncross; Elizabeth Eisenhauer; René O Mirimanoff Journal: N Engl J Med Date: 2005-03-10 Impact factor: 91.245
Authors: Rebecca J Critchley-Thorne; Diana L Simons; Ning Yan; Andrea K Miyahira; Frederick M Dirbas; Denise L Johnson; Susan M Swetter; Robert W Carlson; George A Fisher; Albert Koong; Susan Holmes; Peter P Lee Journal: Proc Natl Acad Sci U S A Date: 2009-05-18 Impact factor: 11.205
Authors: Jedd D Wolchok; James P Allison; Dmitriy Zamarin; Rikke B Holmgaard; Sumit K Subudhi; Joon Seok Park; Mena Mansour; Peter Palese; Taha Merghoub Journal: Sci Transl Med Date: 2014-03-05 Impact factor: 17.956