Adenovirus as a new agent for multiple myeloma therapies: Opportunities and restrictions

Abstract

Multiple myeloma is a malignancy of B-cells that is characterized by the clonal expansion and accumulation of malignant plasma cells in the bone marrow. This disease remains incurable, and a median survival of 3-5 years has been reported with the use of current treatments. Viral-based therapies offer promising alternatives or possible integration with current therapeutic regimens. Among several gene therapy vectors and oncolytic agents, adenovirus has emerged as a promising agent, and it is already being used for the treatment of solid tumors in humans. The main concern with the clinical use of this vector has been its high immunogenicity; adenovirus is often able to induce a strong immune response in the host. Furthermore, new limitations in the efficacy of this therapy, intrinsic to the nature of tumor cells, have been recently observed. For example, our group showed a strong antiviral phenotype in vitro and in vivo in a subset of tumors, shedding new insights that may explain the partial failure of clinical trials based on this promising new therapy. In this review, we describe novel therapeutic approaches that implement viral-based treatments in hematological malignancies and address the novelty as well as the possible limitations of these new therapies, especially in the context of the use of adenoviral vectors for treating multiple myeloma.

PI3K inhibitor LY294002 inhibits activation of the Akt/mTOR pathway induced by an oncolytic adenovirus expressing TRAIL and sensitizes multiple myeloma cells to the oncolytic virus

“…The oncolytic adenovirus is a potent member of a potentially new class of antitumor agents that has been previously demonstrated to have activity in MM (27)(28)(29). Among the viruses used for virotherapy of MM, different serotypes of adenovi- ruses have been studied, with the goal of finding a translational application for the treatment of myeloma progressing on prior therapy (30,31).…”

Myxoma Virus Induces Ligand Independent Extrinsic Apoptosis in Human Myeloma Cells

“…Treatment with these viruses, including: reovirus 11, 12 , recombinant measles 13-15 , vesicular stomatitis virus 16-18 , and adenovirus 19, 20 , is highly cancer specific, reducing the chances of off target toxicities. Additionally, oncolytic viruses often eliminate infected cancer cells through virally distinct mechanisms, which makes them particularly attractive for the treatment of relapsed and/or refractory MM patients.…”

Bovine pestivirus is a new alternative virus for multiple myeloma oncolytic virotherapy

“…Most of the data published reported the use of human MV to kill MM cell [31]. More recently, other virus as reovirus, myxoma, and adenovirus were reported to have oncolytic activity in MM cells [12,32,33]. MV interacts with CD46 to enter into MM cells and to induce a cytopathic effect [15].…”