Rabbit virus could treat multiple myeloma
Researchers have taken a novel approach to treating multiple myeloma: the introduction of the rabbit-killing myxoma virus (MYXV).
Multiple myeloma (MM) is a cancer of plasma B cells, a cell type within the immune system. It is the second most common blood cancer and remains difficult to treat. Most patients succumb to disease relapse either from reinfusion of cancerous cells during stem cell transplant or expansion of drug-resistant disease after chemotherapy.
For the past several years, Assistant Professor Eric Bartee has been using MYXV to treat MM in cell culture. MYXV exclusively infects rabbits and is therefore non-infectious to humans. However, Bartee and his colleagues at the Medical University of South Carolina (MUSC) have found that MYXV is able to kill human MM cells.
Stem cell transplants, using a patient’s own stem cells, are currently used as a treatment for MM, but patients often relapse from residual cancer cells within the transplant sample. Bartee showed that treatment with MYXV was successful in eradicating MM cells in patients’ stem cell samples prior to re-engraftment, thereby preventing relapse of MM.
Bartee and his colleagues recently took this one step further by assessing whether treatment with MYXV also has a benefit on disease outside the context of transplantation. Using a preclinical mouse model, they showed that systemic treatment with MYXV reduced tumour burden and led to a modest decrease in disease progression in 66% of mice. In 25% of mice, there was a complete eradication of disease with no evidence of relapse.
“What I thought was really interesting here was that we could actually get rid of disease and it didn’t appear to ever come back,” said Bartee, who published the results in the journal Molecular Therapy — Oncolytics.
Since MYXV does not replicate in MM cells, it was suggested that eradication of disease was caused by the host’s immune system. Investigation of the bone marrow showed that it was unaffected by treatment with MYXV. This suggested that the immune system remained functional and could combat the cancer cells. Indeed, treatment with MYXV led to an increase in CD8+ T cells, a type of white blood cell, within the bone marrow compartment, indicating a strong antitumour response.
One advantage of treating MM with MYXV is that the response rate observed in the study is not mediated by the virus — it is actually mediated by the patient’s own immune system. Combining MYXV treatment with other immunomodulatory therapies that have been shown to boost antitumour response could provide a novel treatment regimen that improves patient outcome compared to the current treatment model.
Another advantage is that it is extremely difficult for myeloma to develop resistance to killing by MYXV. One of the challenges with standard chemotherapeutic agents is that many tumours often develop resistance through small changes in the cell, leading to relapse of disease. Because MYXV has evolved for thousands of years to override anything the cell can do, there is no real evidence that tumours can develop resistance to oncolytic infections.
But while this preclinical work suggests that MYXV has the potential to cure some patients of MM, there are many hurdles that need to be overcome before this option becomes available — such as large-scale production of a clinical-grade virus and generating a high response rate in humans.
“I think the major next question is ‘How do you get that response rate from 25% to 50% to 80% to 100%?’” said Bartee.
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