Oncolytic viruses, such as the rabbit-specific myxoma virus (MYXV), represent promising, novel methods to treat patients diagnosed with cancer. While the field of oncolytics has traditionally focused on solid tumors, our recent data demonstrates that the MYXV can also effectively treat the hematopoietic malignancy multiple myeloma. Specifically, MYXV discriminates myeloma cells from normal cells based on differential binding and subsequently eliminates these cells by inducing a rapid apoptotic response. This results in MYXV therapy completely preventing myeloma relapse associated with contamination of autologous transplant samples as well as eradicating residual myeloma in vivo through an apparent immunological mechanism. Unfortunately, the translation of this promising therapy is currently prevented by a lack of understanding concerning the mechanisms involved in treatment. This lack of understanding raises concerns about the accurate prediction of patient responses as well as the potential for treatment to generate adverse events. We therefore put forth the current proposal designed to advance the use of MYXV in a clinical setting by identifying the molecular mechanisms mediating: 1) the induction of an anti-myeloma immune response by systemic MYXV treatment, 2) the mechanisms mediating resistance of myeloma cells to MYXV therapy, and 3) the role that viral binding plays in delivery of MYXV to sites of residual disease. The successful completion of this project could have a significant impact on public health in a variety of ways. First it would advance the use of MYXV as a promising therapeutic for the treatment of patients with myeloma. Additionally, information generated in this proposal might be used to improve treatments with other oncolytic viruses by shedding light on the mechanisms mediating successful in vivo therapy.

Public Health Relevance

Myxoma virus is a rabbit specific poxvirus which displays curative potential for the treatment of human multiple myeloma in preclinical models. However, the translation of this therapy is hindered by our lack of understanding concerning the molecular mechanisms involved. The current proposal is therefore designed to advance the use of myxoma as a novel treatment for myeloma by enhancing our understanding of the molecular mechanisms involved in treatment and how these mechanisms influence outcomes.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA194090-04
Application #
9604318
Study Section
Developmental Therapeutics Study Section (DT)
Program Officer
Salomon, Rachelle
Project Start
2015-12-01
Project End
2020-11-30
Budget Start
2018-12-01
Budget End
2019-11-30
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Medical University of South Carolina
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29403
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Bartee, Eric; Bartee, Mee Y; Bogen, Bjarne et al. (2016) Systemic therapy with oncolytic myxoma virus cures established residual multiple myeloma in mice. Mol Ther Oncolytics 3:16032