{"title":"Virotherapy as Potential Adjunct Therapy for Graft-Vs-Host Disease.","authors":"Nancy Y Villa, Grant McFadden","doi":"10.1007/s40139-018-0186-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose of review: </strong>This review discusses the pathophysiology, risk factors, and the advances in the prevention or treatment of graft-vs-host disease (GvHD) by exploiting adjunct virotherapy. In addition, nonviral adjunct therapeutic options for the prevention of GvHD in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are discussed. The role of oncolytic viruses to treat different HSCT-eligible hematological cancers is also considered and correlated with the issue of GvHD in the context of allo-HSCT.</p><p><strong>Recent findings: </strong>Emerging therapies focused on the prevention or treatment of GvHD include the use of regulatory T cells (Tregs), mesenchymal stem cells (MSCs), microbiome manipulation, B cell inhibitors, among others. Our lab and others have reported that an oncolytic DNA virus from the <i>Poxviridae</i> family, called myxoma virus (MYXV), not only exhibits oncolytic activity against various hematologic malignancies like multiple myeloma (MM) or acute myeloid leukemia (AML) but also, in addition, ex vivo MYXV treatment of human allogeneic-bone marrow transplants (allo-BMT), or allo-peripheral blood mononuclear cell (allo-PBMC) transplants can abrogate GvHD in xenografted mice without impairing graft-vs-tumor (GvT) effects against residual cancer. To date, this is the first and the only oncolytic virus with a dual potential of mediating oncolysis against a residual cancer target and also inhibiting or preventing GvHD following allo-HSCT.</p><p><strong>Summary: </strong>This review discusses how oncolytic virotherapy can be applied as a potential adjunct therapy for the potential treatment of GvHD. In addition, we highlight major emerging nonviral therapies currently studied for the treatment or prevention of GvHD. We also review the emerging oncolytic virotherapies against different hematological cancers currently eligible for allo-HSCT and highlight the potential role of the oncolytic virus MYXV to decrease GvHD while maintaining or enhancing the positive benefits of GvT.</p>","PeriodicalId":37014,"journal":{"name":"Current Pathobiology Reports","volume":"6 4","pages":"247-263"},"PeriodicalIF":0.0000,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290699/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Pathobiology Reports","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s40139-018-0186-6","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2018/11/19 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose of review: This review discusses the pathophysiology, risk factors, and the advances in the prevention or treatment of graft-vs-host disease (GvHD) by exploiting adjunct virotherapy. In addition, nonviral adjunct therapeutic options for the prevention of GvHD in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are discussed. The role of oncolytic viruses to treat different HSCT-eligible hematological cancers is also considered and correlated with the issue of GvHD in the context of allo-HSCT.
Recent findings: Emerging therapies focused on the prevention or treatment of GvHD include the use of regulatory T cells (Tregs), mesenchymal stem cells (MSCs), microbiome manipulation, B cell inhibitors, among others. Our lab and others have reported that an oncolytic DNA virus from the Poxviridae family, called myxoma virus (MYXV), not only exhibits oncolytic activity against various hematologic malignancies like multiple myeloma (MM) or acute myeloid leukemia (AML) but also, in addition, ex vivo MYXV treatment of human allogeneic-bone marrow transplants (allo-BMT), or allo-peripheral blood mononuclear cell (allo-PBMC) transplants can abrogate GvHD in xenografted mice without impairing graft-vs-tumor (GvT) effects against residual cancer. To date, this is the first and the only oncolytic virus with a dual potential of mediating oncolysis against a residual cancer target and also inhibiting or preventing GvHD following allo-HSCT.
Summary: This review discusses how oncolytic virotherapy can be applied as a potential adjunct therapy for the potential treatment of GvHD. In addition, we highlight major emerging nonviral therapies currently studied for the treatment or prevention of GvHD. We also review the emerging oncolytic virotherapies against different hematological cancers currently eligible for allo-HSCT and highlight the potential role of the oncolytic virus MYXV to decrease GvHD while maintaining or enhancing the positive benefits of GvT.
期刊介绍:
This journal aims to offer expert review articles on the most important recent research pertaining to biological mechanisms underlying disease, including etiology, pathogenesis, and the clinical manifestations of cellular alteration. By providing clear, insightful, balanced contributions, the journal intends to serve those for whom the elucidation of new techniques and technologies related to pathobiology is essential. We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas across the field. Section Editors select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. An Editorial Board of more than 20 internationally diverse members reviews the annual table of contents, ensures that topics include emerging research, and suggests topics of special importance to their country/region. Topics covered may include autophagy, cancer stem cells, induced pluripotential stem cells (iPS cells), inflammation and cancer, matrix pathobiology, miRNA in pathobiology, mitochondrial dysfunction/diseases, and myofibroblast.