The Use of Oncolytic Viruses in the Treatment of Multiple Myeloma

SIMPLE SUMMARY: Multiple myeloma is a type of blood cancer caused by the uncontrolled growth of antibody producing B cells (known as plasma cells) that reside in the bone marrow. It is classed as a largely incurable cancer as whilst patients respond well to initial chemotherapy treatments, unfortunately after periods of disease remission, relapse usually occurs with the emergence of chemotherapy resistance. Therefore, there is a need for new approaches that not only reduce tumour load but also prevent tumour relapse. Oncolytic viruses (OVs) (tumour killing viruses) are being explored as a therapy for various cancers, including multiple myeloma. This review discusses the use of OVs in myeloma in preclinical model systems and early phase clinical trials, and discusses some of the hurdles involved in the translation to myeloma patients. ABSTRACT: Multiple myeloma accounts for 1% of all new cancers worldwide. It is the second most common haematological malignancy and has a low five-year survival rate (53.2%). Myeloma remains an incurable disease and is caused by the growth of malignant plasma cells in the bone marrow. Current anti-myeloma therapies (conventional chemotherapies, immunomodulatory drugs i.e., thalidomide and its’ analogues, proteasome inhibitors, monoclonal antibodies, and radiotherapy) initially substantially debulk tumour burden, but after a period of remission ‘plateau phase’ disease invariably relapses due to tumour recrudescence from foci of minimal residual disease (MRD) and accumulating drug resistance. Therefore, there is a compelling clinical need for the development of novel treatment regimens to target MRD and effectively eliminate all remaining tumour cells. This review will discuss the potential use of oncolytic virus (OV) therapies in the treatment of myeloma. Specifically, it will focus on preclinical studies using DNA viruses (adenovirus (Ad), vaccinia virus (VV), myxoma virus (MYXV), and herpes simplex virus (HSV)), RNA viruses (reovirus (reo), coxsackie virus, measles virus (MV) and bovine viral diarrhoea virus (BVDV), and vesicular stomatitis virus (VSV)), and on four types of viruses (VV, reo, MV-NIS and VSV-IFNβ-NIS) that have been assessed clinically in a small number of myeloma patients.