Ex Vivo Oncolytic Virotherapy with Myxoma Virus Arms Multiple Allogeneic Bone Marrow Transplant Leukocytes to Enhance Graft versus Tumor

Cameron L. Lilly, Nancy Villa, Ana Lemos de Matos, Haider M. Ali, Jess Karan S. Dhillon, Tom Hofland, Masmudur Rahman, Winnie Chan, Bjarne Bogen, Christopher Cogle, Douglas McFadden

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Allogeneic stem cell transplant-derived T cells have the potential to seek and eliminate sites of residual cancer that escaped primary therapy. Oncolytic myxoma virus (MYXV) exhibits potent anti-cancer efficacy against human cancers like multiple myeloma (MM) and can arm transplant-derived T cells to become more effective cancer killers in vitro and in an immunodeficient xenotransplant murine model. Here, we tested ex vivo MYXV virotherapy against residual murine MM in immunocompetent mice using an allogeneic mouse-mouse model. In contrast to all human MM cell lines previously tested, the murine MM cell line tested here was highly resistant to direct MYXV infection and oncolysis in vitro. Despite this in vitro resistance, we found that ex vivo MYXV-armed allogeneic bone marrow (BM) transplantation dramatically ablated pre-seeded residual MM in vivo. Unexpectedly, we show that both neutrophils and activated T cells from the donor function as virus-armed carrier cells, and MYXV-preloaded cells enhanced MM killing. Our results demonstrate a novel therapeutic paradigm for residual cancer, in which multiple classes of allotransplant leukocytes can be armed by MYXV ex vivo to enhance the graft-versus-tumor effects.

Original languageEnglish (US)
Pages (from-to)31-40
Number of pages10
JournalMolecular Therapy - Oncolytics
Volume4
DOIs
StatePublished - Mar 1 2017
Externally publishedYes

Fingerprint

Myxoma virus
Oncolytic Virotherapy
Multiple Myeloma
Leukocytes
Arm
Bone Marrow
Transplants
Neoplasms
Residual Neoplasm
T-Lymphocytes
Oncolytic Viruses
Cell Line
Homologous Transplantation
Virus Diseases
Bone Marrow Transplantation
Neutrophils
Stem Cells
Viruses
Therapeutics

Keywords

  • allogenic transplant
  • MOPC315.BM
  • multiple myeloma
  • myxoma virus
  • neutrophils
  • T cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Ex Vivo Oncolytic Virotherapy with Myxoma Virus Arms Multiple Allogeneic Bone Marrow Transplant Leukocytes to Enhance Graft versus Tumor. / Lilly, Cameron L.; Villa, Nancy; Lemos de Matos, Ana; Ali, Haider M.; Dhillon, Jess Karan S.; Hofland, Tom; Rahman, Masmudur; Chan, Winnie; Bogen, Bjarne; Cogle, Christopher; McFadden, Douglas.

In: Molecular Therapy - Oncolytics, Vol. 4, 01.03.2017, p. 31-40.

Research output: Contribution to journalArticle

Lilly, Cameron L. ; Villa, Nancy ; Lemos de Matos, Ana ; Ali, Haider M. ; Dhillon, Jess Karan S. ; Hofland, Tom ; Rahman, Masmudur ; Chan, Winnie ; Bogen, Bjarne ; Cogle, Christopher ; McFadden, Douglas. / Ex Vivo Oncolytic Virotherapy with Myxoma Virus Arms Multiple Allogeneic Bone Marrow Transplant Leukocytes to Enhance Graft versus Tumor. In: Molecular Therapy - Oncolytics. 2017 ; Vol. 4. pp. 31-40.
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