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Oncolytic Maraba Virus MG1 as a Treatment for Sarcoma
Author(s) -
Le Boeuf Fabrice,
Selman Mohammed,
Son Hwan Hee,
Bergeron Anabel,
Chen Andrew,
Tsang Jovian,
Butterwick Derek,
Arulanandam Rozanne,
Forbes Nicole E.,
Tzelepis Fanny,
Bell John C.,
Werier Joel,
Abdelbary Hesham,
Diallo JeanSimon
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30813
Subject(s) - oncolytic virus , sarcoma , ex vivo , immunotherapy , in vivo , virology , virus , cancer research , immune system , medicine , soft tissue sarcoma , herpes simplex virus , immunology , vaccinia , biology , pathology , microbiology and biotechnology , biochemistry , gene , recombinant dna
The poor prognosis of patients with advanced bone and soft‐tissue sarcoma has not changed in the past several decades, highlighting the necessity for new therapeutic approaches. Immunotherapies, including oncolytic viral (OV) therapy, have shown great promise in a number of clinical trials for a variety of tumor types. However, the effective application of OV in treating sarcoma still remains to be demonstrated. Although few pre‐clinical studies using distinct OVs have been performed and demonstrated therapeutic benefit in sarcoma models, a side‐by‐side comparison of clinically relevant OV platforms has not been performed. Four clinically relevant OV platforms (Reovirus, Vaccinia virus, Herpes‐simplex virus and Rhabdovirus) were screened for their ability to infect and kill human and canine sarcoma cell lines in vitro , and human sarcoma specimens ex vivo . In vivo treatment efficacy was tested in a murine model. The rhabdovirus MG1 demonstrated the highest potency in vitro . Ex vivo , MG1 productively infected more than 80% of human sarcoma tissues tested, and treatment in vivo led to a significant increase in long‐lasting cures in sarcoma‐bearing mice. Importantly, MG1 treatment induced the generation of memory immune response that provided protection against a subsequent tumor challenge. This study opens the door for the use of MG1‐based oncolytic immunotherapy strategies as treatment for sarcoma or as a component of a combined therapy.