Ex vivo virotherapy with myxoma virus does not impair hematopoietic stem and progenitor cells

Villa, Nancy Y.; Bais, Swarna; Chan, Winnie; Meacham, Amy; Wise, Elizabeth; Rahman, Masmudur M.; Moreb, Jan S.; Rosenau, Emma; Wingard, John R.; McFadden, Grant; Cogle, Christopher R.

doi:10.1016/j.jcyt.2015.12.007

Cited by 21 publications

(16 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results indicated that, while CD138 hi cells in MOPC-315 engrafted mice displayed high levels of Cy5 fluorescence after ex vivo viral adsorption, this fluorescent shift was not seen on CD138 hi cells from MOPC-315.BM engrafted mice (Figure 5b) indicating that the inability of these cells to support MYXV binding was maintained in vivo . Consistent with previous reports, 20,21 a significant fluorescent shift was also observed on CD138 lo normal plasma cells indicating that the virus is also capable of binding certain nonmalignant B cell populations. To determine whether MYXV treatment might impact MM engraftment indirectly, we next asked whether viral injection would have any impact on MRD established with binding deficient MOPC-315.BM cells.…”

Section: Resultssupporting

confidence: 92%

“…While MYXV is unable to infect the majority of normal human hematopoietic cells, one exception to this rule is CD19 + B cells. 21 Thus, one possible explanation for our results was that virally induced anti-MM immune responses were actually generated through killing of normal resident B cells, a mechanism which would likely also produce autoimmune like toxicities. Interestingly, while our data indicates that MYXV is able to bind CD138 lo normal plasma cells in vivo (Figure 5b) the induction of anti-MM immune responses requires direct interaction of MYXV with CD138 hi malignant MM cells.…”

Section: Discussionmentioning

confidence: 85%

See 1 more Smart Citation

Systemic therapy with oncolytic myxoma virus cures established residual multiple myeloma in mice

Bartee

Bogen

et al. 2016

Molecular Therapy - Oncolytics

View full text Add to dashboard Cite

Multiple myeloma is an incurable malignancy of plasma B-cells. Traditional chemotherapeutic regimes often induce initial tumor regression; however, virtually all patients eventually succumb to relapse caused by either reintroduction of disease during autologous transplant or expansion of chemotherapy resistant minimal residual disease. It has been previously demonstrated that an oncolytic virus known as myxoma can completely prevent myeloma relapse caused by reintroduction of malignant cells during autologous transplant. The ability of this virus to treat established residual disease in vivo, however, remained unknown. Here we demonstrate that intravenous administration of myxoma virus into mice bearing disseminated myeloma results in the elimination of 70–90% of malignant cells within 24 hours. This rapid debulking was dependent on direct contact of myxoma virus with residual myeloma and did not occur through destruction of the hematopoietic bone marrow niche. Importantly, systemic myxoma therapy also induced potent antimyeloma CD8+ T cell responses which localized to the bone marrow and were capable of completely eradicating established myeloma in some animals. These results demonstrate that oncolytic myxoma virus is not only effective at preventing relapse caused by reinfusion of tumor cells during stem cell transplant, but is also potentially curative for patients bearing established minimal residual disease.

show abstract

Section: Resultssupporting

confidence: 92%

Section: Discussionmentioning

confidence: 85%

Systemic therapy with oncolytic myxoma virus cures established residual multiple myeloma in mice

Bartee

Bogen

et al. 2016

Molecular Therapy - Oncolytics

View full text Add to dashboard Cite

show abstract

“…Myxoma virus (MYXV) is a distinct Leporipoxvirus initially identified as the causative agent for myxomatosis, a lethal disease specific to European rabbit strains (oryctolagus cuniculus) but nonpathogenic for other mammals (27,28). Based on this observation, MYXV was released in Australia in the 1950s to control feral rabbits (29).…”

Section: Sclc Patient Biopsy Specimens and An Optimized Genetically Ementioning

confidence: 99%

Oncolytic virotherapy for small-cell lung cancer induces immune infiltration and prolongs survival

Kellish¹,

Shabashvili²,

Rahman³

et al. 2019

Journal of Clinical Investigation

Self Cite

View full text Add to dashboard Cite

“…A prototypic member of the Leporipoxvirus genus of the Poxviridae family, MYXV causes the lethal disease called myxomatosis in European rabbits ( Oryctolagus cuniculus ) [ 201 , 202 ]. Interestingly, the virus is non-pathogenic for any host outside the lagomorph family, failing to propagate in any non-rabbit species, including immunodeficient mice and humans [ 201 , 203 , 204 ]. Despite its narrow host range in nature, MYXV productively infects and replicates in a wide diversity of human cancer cells.…”

Section: Alternative and Novel Strategies To Inhibit Graft- mentioning

confidence: 99%

Therapeutics for Graft-versus-Host Disease: From Conventional Therapies to Novel Virotherapeutic Strategies

Villa

Rahman

McFadden

et al. 2016

Viruses

Self Cite

View full text Add to dashboard Cite

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has a curative potential for many hematologic malignancies and blood diseases. However, the success of allo-HSCT is limited by graft-versus-host disease (GVHD), an immunological syndrome that involves inflammation and tissue damage mediated by donor lymphocytes. Despite immune suppression, GVHD is highly incident even after allo-HSCT using human leukocyte antigen (HLA)-matched donors. Therefore, alternative and more effective therapies are needed to prevent or control GVHD while preserving the beneficial graft-versus-cancer (GVC) effects against residual disease. Among novel therapeutics for GVHD, oncolytic viruses such as myxoma virus (MYXV) are receiving increased attention due to their dual role in controlling GVHD while preserving or augmenting GVC. This review focuses on the molecular basis of GVHD, as well as state-of-the-art advances in developing novel therapies to prevent or control GVHD while minimizing impact on GVC. Recent literature regarding conventional and the emerging therapies are summarized, with special emphasis on virotherapy to prevent GVHD. Recent advances using preclinical models with oncolytic viruses such as MYXV to ameliorate the deleterious consequences of GVHD, while maintaining or improving the anti-cancer benefits of GVC will be reviewed.

show abstract

Ex vivo virotherapy with myxoma virus does not impair hematopoietic stem and progenitor cells

Cited by 21 publications

References 17 publications

Systemic therapy with oncolytic myxoma virus cures established residual multiple myeloma in mice

Systemic therapy with oncolytic myxoma virus cures established residual multiple myeloma in mice

Oncolytic virotherapy for small-cell lung cancer induces immune infiltration and prolongs survival

Therapeutics for Graft-versus-Host Disease: From Conventional Therapies to Novel Virotherapeutic Strategies

Contact Info

Product

Resources

About