Advances in viral oncolytics for treatment of multiple myeloma – a focused review

ABSTRACT

Introduction

Oncolytic viruses are genetically engineered viruses that target myeloma-affected cells by detecting specific cell surface receptors (CD46, CD138), causing cell death by activating the signaling pathway to induce apoptosis or by immune-mediated cellular destruction.

Areas covered

This article summarizes oncolytic virotherapy advancements such as the therapeutic use of viruses by targeting cell surface proteins of myeloma cells as well as the carriers to deliver viruses to the target tissues safely. The major classes of viruses that have been studied for this include measles, myxoma, adenovirus, reovirus, vaccinia, vesicular-stomatitis virus, coxsackie, and others. The measles virus acts as oncolytic viral therapy by binding to the CD46 receptors on the myeloma cells to utilize its surface H protein. These H-protein and CD46 interactions lead to cellular syncytia formation resulting in cellular apoptosis. Vesicular-stomatitis virus acts by downregulation of anti-apoptotic factors (Mcl-2, BCL-2). Based upon the published literature searches till December 2020, we have summarized the data supporting the advances in viral oncolytic for the treatment of MM.

Expert opinion

Oncolytic virotherapy is an experimental approach in multiple myeloma (MM); many issues need to be addressed for safe viral delivery to the target tissue

KEYWORDS:

• Multiple myeloma
• oncolytic virotherapy
• measles virus
• reovirus
• vesicular-stomatitis virus
• myxoma virus
• adenovirus
• vaccinia virus
• coxsackie virus
• mengo virus
• bovine virus

Article Highlights

• Oncotic virotherapy is a new class of therapy deploying natural or genetically engineered oncolytic viruses that have been tested in relapsed refractory MM alone or combined with conventional treatment options.

• Oncoloytic viral therapy trials have utilized Bovine virus, Myxoma virus, Mengovirus, Adenovirus, Measles virus, Vaccinia virus, Reovirus, Vesicular-stomatitis virus, and Coxsackie viruses.

• Measles virus, vesiculo-stomatitis virus, and reovirus have entered phase-1 of clinical trials for oncolytic viral therapies.

• Circulating immunoglobulins against the virus because of past infection or vaccination against the pathogen or immune mediating organs response, are some of the significant challenges faced by these therapies.

Authorship statement

Ayesha Sarwar, Mobeen Zaka Haider, and Zahoor Ahmed designed the study. All authors performed the study, literature review, analyzed the data, and wrote the paper.

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.