Reovirus as a successful ex vivo purging modality for multiple myeloma

Thirukkumaran, Chandini M.; Zhong, Shuming; Luider, Joanne; Kopciuk, Karen; Bahlis, Nizar J.; Neri, Paola; Pho, Mark; Stewart, Douglas A.; Mansoor, Adnan; Morris, Don

doi:10.1038/bmt.2013.130

Cited by 22 publications

(23 citation statements)

References 23 publications

(40 reference statements)

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“…Oncolytic viruses are very attractive cancer therapies since they replicate and may continue to spread and infect more tumor cells. MRV has been demonstrated to target and kill MM, and a phase I clinical trial has recently been initiated [18, 29]. Thirukkumaran et al demonstrated that apoptosis induced by MRV infection contributes to oncolysis of human multiple myeloma cell lines (HMCL) [30].…”

Section: Viral Induction Of Autophagy In Oncolysismentioning

confidence: 99%

The Interplay of Reovirus with Autophagy

Chiu

Richart

Lin

et al. 2014

BioMed Research International

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Autophagy participates in multiple fundamental physiological processes, including survival, differentiation, development, and cellular homeostasis. It eliminates cytoplasmic protein aggregates and damaged organelles by triggering a series of events: sequestering the protein substrates into double-membrane vesicles, fusing the vesicles with lysosomes, and then degrading the autophagic contents. This degradation pathway is also involved in various disorders, for instance, cancers and infectious diseases. This paper provides an overview of modulation of autophagy in the course of reovirus infection and also the interplay of autophagy and reovirus.

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Section: Viral Induction Of Autophagy In Oncolysismentioning

confidence: 99%

The Interplay of Reovirus with Autophagy

Chiu

Richart

Lin

et al. 2014

BioMed Research International

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“…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.…”

Section: Introductionmentioning

confidence: 99%

Myxoma Virus Induces Ligand Independent Extrinsic Apoptosis in Human Myeloma Cells

Bartee

Dunlap

Bartee

2016

Clinical Lymphoma Myeloma and Leukemia

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Introduction Multiple myeloma is a clonal malignancy of plasma B cells. While recent advances have improved overall prognosis, virtually all myeloma patients still succumb to relapsing disease. Therefore, novel therapies to treat this disease remain urgently needed. We have recently demonstrated that treatment of human multiple myeloma cells with an oncolytic virus known as myxoma results in rapid cell death even in the absence of viral replication; however, the specific mechanisms and pathways involved remain unknown. Materials and Methods To determine how Myxoma virus eliminates human multiple myeloma cells, we queried the apoptotic pathways which were activated following viral infection using immunoblot and other cell biology approaches. Results Our results indicate that myxoma virus infection initiates apoptosis in multiple myeloma cells through activation of the extrinsic initiator caspase-8. Caspase-8 activation subsequently results in cleavage of Bid and loss of mitochondrial membrane potential causing secondary activation of caspase-9. Activation of caspase-8 appears to be independent of extrinsic death ligands and instead correlates with depletion of cellular inhibitors of apoptosis. We hypothesize that this depletion results from virally mediated host-protein shutoff since a myxoma construct which overexpresses the viral decapping enzymes displays improved oncolytic potential. Conclusion Taken together, these results suggest that myxoma virus eliminates human multiple myeloma cells through a pathway unique to oncolytic poxviruses making it an excellent therapeutic option for the treatment of relapsed or refractory patients.

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“…These data suggest that reovirus maybe more effective as part of combination therapy, in particular with agents upregulating JAM-A expression on MM cells [188]. The ability of reovirus to selectively infect MM cells found at low levels in mixtures of normal bone marrow aspirates has led to the proposal of it being used as a purging agent for stem cell harvest prior to ASCT [189]. Further studies are required to define the optimal role of this agent in MM OV therapy.…”

Section: Reovirusmentioning

confidence: 99%