Potential of oncolytic viruses in the treatment of multiple myeloma

Abstract

Multiple myeloma (MM) is a clonal malignancy of plasma cells that is newly diagnosed in ~30,000 patients in the US each year. While recently developed therapies have improved the prognosis for MM patients, relapse rates remain unacceptably high. To overcome this challenge, researchers have begun to investigate the therapeutic potential of oncolytic viruses as a novel treatment option for MM. Preclinical work with these viruses has demonstrated that their infection can be highly specific for MM cells and results in impressive therapeutic efficacy in a variety of preclinical models. This has led to the recent initiation of several human trials. This review summarizes the current state of oncolytic therapy as a therapeutic option for MM and highlights a variety of areas that need to be addressed as the field moves forward.

Immunotherapy in Multiple Myeloma

“…Serotypes 6, 26 and 48 were found to have anti-MM activity, while serotypes 11, 35, 40 and 41 were toxic to PBMCs but not MM cells [190]. The explanation for the differential efficacy between serotypes maybe more related to replication kinetics than viral adsorption or receptor upregulation as described for other viruses [177]. The in vivo efficacy of adenovirus therapy has been modest, leading to attempts at modifying the virus to enhance its killing capability [177,190].…”

“…Several naturally occurring viruses have been used as agents for OV therapy, with modifications to enhance their specificity for tumor cells. A number of characteristics make MM an attractive target for OV [177]. Overexpression of specific cell surface receptors allows some viruses easier access to MM cells while altered IFN-γ and protein kinase R (PKR) activity render MM cells more suitable for viral replication [177,178].…”

“…The measles virus (MV) is one of the best studied agents for OV in hematologic malignancies [177]. MM cells significantly overexpress the MV receptor CD46 compared to normal hematopoietic cells, making them more susceptible to infection by MV [179].…”

“…The mechanism behind MV-mediated MM cell death is not fully understood. Lytic viral replication is likely to be a major mechanism while formation of syncitia may also contribute [177]. MV therapy has shown significant efficacy in patient-derived xenograft ( PDX) models of MM [180].…”

“…Furthermore, antibodies against MV are passively transferred to the mice when human MM cells are delivered via tail vein injection, resulting in some neutralization of MV in the PDX [182]. The use of immunodeficient PDX models also hampers the study of oncolytic immunotherapy induced by MV [177]. Despite these hurdles, MV has progressed into clinical trials for relapsed/refractory MM.…”