Elsevier

Cytokine & Growth Factor Reviews

Volume 56, December 2020, Pages 39-48
Cytokine & Growth Factor Reviews

Engineering and combining oncolytic measles virus for cancer therapy

https://doi.org/10.1016/j.cytogfr.2020.07.005Get rights and content

Highlights

  • Vaccine strain-derived, oncolytic measles viruses (oMeV) are promising oncolytic immunotherapeutics.

  • They have an excellent safety record and can be genetically engineered for superior efficacy and tumor-specificity.

  • oMeV alone or in combination with additional treatment modalities have demonstrated efficacy in pre-clinical tumor models.

  • oMeV are currently being evaluated in early clinical trials as novel therapeutic agents for treatment of human cancer.

Abstract

Cancer immunotherapy using tumor-selective, oncolytic viruses is an emerging therapeutic option for solid and hematologic malignancies. A considerable variety of viruses ranging from small picornaviruses to large poxviruses are currently being investigated as potential candidates. In the early days of virotherapy, non-engineered wild-type or vaccine-strain viruses were employed. However, these viruses often did not fully satisfy the major criteria of safety and efficacy. Since the advent of reverse genetics systems for manipulating various classes of viruses, the field has shifted to developing genetically engineered viruses with an improved therapeutic index. In this review, we will summarize the concepts and strategies of multi-level genetic engineering of oncolytic measles virus, a prime candidate for cancer immunovirotherapy. Furthermore, we will provide a brief overview of measles virus-based multimodal combination therapies for improved tumor control and clinical efficacy.

Abbreviations

5-FUMP
5-fluorouridine monophosphate
Ad
adenovirus
ATP
adenosine triphosphate
BiTE
bi-specific T-cell engager
CCNU
lomustine
CDV
canine distemper virus
CEA
carcinoembryonic antigen
CHIK
chikungunya
CPA
cyclophosphamide
CTLA-4
cytotoxic T-lymphocyte-associated protein 4
DCA
dichloroacetate
EGFR
epidermal growth factor receptor
EMA
European Medicines Agency
F
fusion
FDA
U.S. Food and Drug Administration
FMG
fusogenic membrane glycoprotein
GA
geldanamycin
GM-CSF
granulocyte-macrophage colony-stimulating factor
H
hemagglutinin
HCC
hepatocellular carcinoma
HADC
histone deacetylase
HSV
herpes simplex virus
i.p.
intraperitoneal
i.t.
intratumoral
ICI
immune checkpoint inhibition
IDO
indoleamine 2,3-dioxygenase
IFN
interferon
IL
interleukin
IRF
interferon regulatory factor
MAVS
mitochondrial antiviral signaling protein
MCP
membrane cofactor protein
MeV
measles virus
MOI
multiplicity of infection
NIS
sodium iodide symporter
NK
natural killer
OV
oncolytic virus
PD
programmed cell death
PNP
purine nucleoside phosphorylase
PVRL4
poliovirus receptor-like 4
RT
radiotherapy
SCD
super cytosine deaminase
scFv
single-chain variable fragment
SCID
severe combined immunodeficient
SLAMF1
signaling lymphocytic activation molecule, family member 1
TIL
tumor infiltrating lymphocyte
TME
tumor microenvironment
TMZ
temozolomide

Keywords

Measles virus
Genetic engineering
Virotherapy
Oncolytic virus
Immunotherapy
Combination therapy

Cited by (0)

Mathias F. Leber, MD, PhD, is a clinician-scientist, and currently works as a Senior Research Associate and Head of Laboratory at the Ottawa Hospital Research Institute (Cancer Therapeutics Program). His main research interests are novel immuno-virotherapy approaches and the genetic engineering of oncolytic viruses using small RNAs.

Serge Neault is a Ph.D. student at the University of Ottawa in Ottawa, Canada. His current research interest is in the design of oncolytic viruses for a novel treatment of cancers.

Elise Jirovec recently completed her Bachelor’s degree in Biopharmaceutical Science at the University of Ottawa and is starting her Master’s degree in Innovative Medicine at Heidelberg University. Her current research interest is in the design of a novel virotherapy for cancer treatment.

Russell Barkley is a Master’s student at the University of Ottawa with a deep curiosity for all things unknown. He enjoys creating fresh ideas and being puzzled by new discoveries. Outside of the laboratory he can be found at the local ice hockey rink.

Aida Said obtained her MSc. in Neuroscience from the Faculty of Medicine, University of Ottawa. She is currently pursuing a PhD degree in Microbiology and Immunology at the Faculty of Medicine, University of Ottawa. Her research interest is focused on developing treatments for cancer by combining oncolytic measles virus with kinase inhibitors.

John C. Bell, PhD, is a Senior Scientist in the Cancer Therapeutics Program at the Ottawa Hospital Research Institute and a Professor of Medicine at the University of Ottawa. He is also the Scientific Director of BioCanRx, a network of scientists, clinicians, cancer stakeholders, academic institutions, NGOs and industry partners aiming at the development of leading-edge immune oncology therapies. John is also a co-founder of Turnstone Biologics, a company developing viral immunotherapeutics against cancer. Since 2012, he heads the Terry Fox-funded Canadian Oncolytic Virus Consortium, which is developing virus-based cancer therapeutics, and he is the Director of the Biotherapeutics Program for the Ontario Institute for Cancer Research. In addition, John is the Scientific Director of the National Centre of Excellence for the development of Biotherapeutics for Cancer Therapy and a fellow of the Royal Society of Canada.

Guy Ungerechts, MD, PhD, is the Deputy Director of the Department of Medical Oncology at the Heidelberg University Hospital in Heidelberg, Germany, and Head of the Clinical Cooperation Unit “Virotherapy” at the German Cancer Research Center in Heidelberg, Germany. He is also the co-founder of CanVirex, a spin-off company from the University Hospital Heidelberg, focused on the development of novel immunovirotherapies. Guy is an affiliated investigator at the Ottawa Hospital Research Institute (Cancer Therapeutics Program). His main research interest is the translation of oncolytic immunotherapies from bench to bedside.

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