Oncolytic viral purging of leukemic hematopoietic stem and progenitor cells with Myxoma virus |
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| Authors: | Masmudur M Rahman Gerard J Madlambayan Christopher R Cogle Grant McFadden |
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| Institution: | 1. Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA;2. Division of Hematology/Oncology, Department of Medicine, University of Florida, Gainesville, FL 32610, USA;1. Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA;1. Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32611, USA;2. College of Agriculture and Life Sciences, University of Florida, Gainesville, FL 32611, USA;3. Department of Experimental Immunology, Academic Medical Center, Amsterdam, 1105 the Netherlands;4. DNAtrix, Inc., Houston, TX 77021, USA;5. Centre for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital, 0313 Oslo, Norway;6. KG Jebsen Centre for Influenza Vaccine Research, University of Oslo, 0313 Oslo, Norway;7. Department of Medicine, University of Florida, Gainesville, FL 32611, USA;1. Swim Across America Laboratory, Immunology Program, Sloan-Kettering Institute for Cancer Research, New York, New York, USA;2. Department of Medicine, Gynecologic Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA;3. Department of Medicine, Melanoma and Immunotherapy Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA;4. Ludwig Center for Cancer Immunotherapy at Memorial Sloan-Kettering Cancer Center, New York, New York, USA;5. Weill Cornell Medical College and Graduate School of Medical Sciences of Cornell University, New York, New York, USA;1. Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA;2. Department of Mathematics, University of Houston, TX 77204, USA;3. Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA;1. Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA;2. University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA;3. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA |
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| Abstract: | High-dose chemotherapy and radiation followed by autologous blood and marrow transplantation (ABMT) has been used for the treatment of certain cancers that are refractory to standard therapeutic regimes. However, a major challenge with ABMT for patients with hematologic malignancies is disease relapse, mainly due to either contamination with cancerous hematopoietic stem and progenitor cells (HSPCs) within the autograft or the persistence of residual therapy-resistant disease niches within the patient. Oncolytic viruses represent a promising therapeutic approach to prevent cancer relapse by eliminating tumor-initiating cells that contaminate the autograft. Here we summarize an ex vivo “purging” strategy with oncolytic Myxoma virus (MYXV) to remove cancer-initiating cells from patient autografts prior to transplantation. MYXV, a novel oncolytic poxvirus with potent anti-cancer properties in a variety of in vivo tumor models, can specifically eliminate cancerous stem and progenitor cells from samples obtained from acute myelogenous leukemia (AML) patients, while sparing normal CD34+ hematopoietic stem and progenitor cells capable of rescuing hematopoiesis following high dose conditioning. We propose that a broader subset of patients with intractable hematologic malignancies who have failed standard therapy could become eligible for ABMT when the treatment schema is coupled with ex vivo oncolytic therapy. |
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