Oncolytic Viruses for Multiple Myeloma Therapy

Abstract

Although recent treatment advances have improved outcomes for patients with multiple myeloma (MM), the disease frequently becomes refractory to current therapies. MM thus remains incurable for most patients and new therapies are urgently needed. Oncolytic viruses are a promising new class of therapeutics that provide tumor-targeted therapy by specifically infecting and replicating within cancerous cells. Oncolytic therapy yields results from both direct killing of malignant cells and induction of an anti-tumor immune response. In this review, we will describe oncolytic viruses that are being tested for MM therapy with a focus on those agents that have advanced into clinical trials.

Immunotherapy in Multiple Myeloma

“…Coxsackie virus causes mild respiratory disease in humans [200]. It has shown promising pre-clinical activity in cell lines and murine models [201].…”

“…The development of host immunity against viruses is an important barrier to clinical application of OV [177,200]. Suppressing the host immune response with cyclophosphamide has been proposed as a means to overcome this hurdle [203].…”

“…Suppressing the host immune response with cyclophosphamide has been proposed as a means to overcome this hurdle [203]. As cyclophosphamide is commonly used in MM treatment protocols, it is an attractive option for combination therapy [200]. Combining IMiDs with OV may also be a promising option for future clinical trials given that OV augments the immune response and may potentially enhance the activity of IMiDs [200].…”

“…As cyclophosphamide is commonly used in MM treatment protocols, it is an attractive option for combination therapy [200]. Combining IMiDs with OV may also be a promising option for future clinical trials given that OV augments the immune response and may potentially enhance the activity of IMiDs [200]. Given the evidence that reovirus disrupts the unfolded protein response, combination of this agent with proteasome inhibitors is an attractive option for further studies.…”

“…Given the evidence that reovirus disrupts the unfolded protein response, combination of this agent with proteasome inhibitors is an attractive option for further studies. Phase 1 clinical trials are currently evaluating this combination in relapsed and/or refractory MM (NCT02514382) [200].…”