The Use of Oncolytic Viruses in the Treatment of Multiple Myeloma

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.

A new strategy for treating colorectal cancer: Regulating the influence of intestinal flora and oncolytic virus on interferon

“…Another way to inhibit IFN-I is to produce bait protein to bind specifically with IFN, to prevent IFN from binding with cell receptors and starting a signal cascade reaction. For example, an oncolytic pox virus (VV) encodes B18R, 172 a king of soluble IFN-I receptors on infected cells, thus preventing IFN from combining with cell receptors. The protein B18R of Wyeth strain OVJx594 of oncolytic pox virus is naturally truncated, 173 which seriously reduces its affinity for IFN.…”

“… 171 2017 oncolytic pox virus VV encodes B18R, which prevents IFN from binding to the fine-cell receptor Stewart et al. 172 2021 the B18R protein of OV Jx594 is naturally truncated, reducing its affinity for IFN Sun et al. 173 2019 Enhance the anti-tumor effect of IFN-II herpes simplex virus HSV-1 stimulates NK cells to release IFN-II through TLR2/NF-κB signaling pathway Wang et al.…”

Immunotherapy approaches for hematological cancers

“…The use of OVs as a treatment for hematological cancers has aroused the interest of many researchers because it has shown to be capable of producing remission in different types of cancer, including multiple myeloma ( Meyers et al., 2017 ; Stewart et al., 2021 ). In this particular case, current preclinical and clinical efforts are focused on RNA viruses (measles virus, vesicular stomatitis virus and reovirus) and DNA viruses (adenovirus, vaccinia virus and myxoma virus) ( Cook et al., 2021 ).…”

Myxoma Virus Combination Therapy Enhances Lenalidomide and Bortezomib Treatments for Multiple Myeloma

“…Hematological malignancies, including lymphoma, leukemia, and multiple myeloma, have seen a recent rise in occurrence and mortality rates [1]. Multiple myeloma (MM), characterized as a malignancy originating from differentiated B cells, is the second most prevalent hematological cancer and constitutes approximately 1% of all newly diagnosed cancers [2]. The primary feature of MM is the excessive proliferation of malignant plasma cells (MPCs) in the bone marrow, which leads to clinical manifestations including skeletal complications, immunodeficiency, and anemia [3].…”