Potential and clinical translation of oncolytic measles viruses

ABSTRACT

Introduction: Oncolytic viruses represent a novel treatment modality that is unencumbered by the standard resistance mechanisms limiting the therapeutic efficacy of conventional antineoplastic agents. Attenuated engineered measles virus strains derived from the Edmonston vaccine lineage have undergone extensive preclinical evaluation with significant antitumor activity observed in a broad range of preclinical tumoral models. These have laid the foundation for several clinical trials in both solid and hematologic malignancies, which have demonstrated safety, biologic activity and the ability to elicit antitumor immune responses.

Areas covered: This review examines the published preclinical data which supported the clinical translation of this therapeutic platform, reviews the available clinical trial data and expands on ongoing phase II testing. It also looks at approaches to optimize clinical applicability and offers future perspectives.

Expert opinion: Reverse genetic engineering has allowed the generation of oncolytic MV strains retargeted to increase viral tumor specificity, or armed with therapeutic and immunomodulatory genes in order to enhance anti-tumor efficacy. Continuous efforts focusing on exploring methods to overcome resistance pathways and determining optimal combinatorial strategies will facilitate further development of this encouraging antitumor strategy.

KEYWORDS:

• Virotherapy
• measles
• MV-CEA
• MV-NIS
• oncolytic
• Edmonston

Article highlights

• Preclinical testing has demonstrated potent antitumor effect of oncolytic measles virus strains in a wide range of hematologic and solid tumor models.

• Retargeting of oncolytic measles virus strains by displaying single chain antibodies or cytokine ligands and ablating entry through natural receptors has been successfully accomplished.

• Oncolytic measles virus strains can be modified to express therapeutic transgenes such as prodrug converting enzymes or immunomodulatory cytokines.

• Reported and ongoing clinical trials have shown that oncolytic measles virus strains can be safely administered to patients and have yielded encouraging preliminary results.

• Measles virus induced oncolytic cell death is immunogenic. Combination of measles virotherapy with immune checkpoint inhibitors results in synergistic activity setting the stage for translational applications

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

The work was in part funded by National Cancer Institute grants K12 CA090628, P50 CA108961, P50 CA116201, P50 CA136393, R01 CA154348, R01 CA136547.