Journal
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Volume 18, Issue 10, Pages 1540-1551Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2012.04.004
Keywords
Ex vivo purging; Myxoma virus; Viral oncolytics; Multiple myeloma; Autologous hematopoietic stem cell transplantation
Categories
Funding
- University of Florida-College of Medicine
- Florida Department of Health Bankhead Coley Research Program [1BT02]
- STOP! Children's Cancer, Inc.
- Leukemia & Lymphoma Society
- [NIH-R01 CA138541]
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Autologous stem cell transplantation and novel therapies have improved overall survival of patients with multiple myeloma; however, most patients relapse and eventually succumb to their disease. Evidence indicates that residual cancer cells contaminate autologous grafts and may contribute to early relapses after autologous stem cell transplantation. Here, we demonstrate that ex vivo treatment with an oncolytic poxvirus called myxoma virus results in specific elimination of human myeloma cells by inducing rapid cellular apoptosis while fully sparing normal hematopoietic stem and progenitor cells. The specificity of this elimination is based on strong binding of the virus to myeloma cells coupled with an inability of the virus to bind or infect CD34(+) hematopoietic stem and progenitor cells. These 2 features allow myxoma to readily identify and distinguish even low levels of myeloma cells in complex mixtures. This ex vivo rabbit-specific oncolytic poxvirus called myxoma virus treatment also effectively inhibits systemic in vivo engraftment of human myeloma cells into immunodeficient mice and results in efficient elimination of primary CD138(+) myeloma cells contaminating patient hematopoietic cell products. We conclude that ex vivo myxoma treatment represents a safe and effective method to selectively eliminate myeloma cells from hematopoietic autografts before reinfusion. Biol Blood Marrow Transplant 18: 1540-1551 (2012) (C) 2012 American Society for Blood and Marrow Transplantation
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