Systemic Therapy with Rabbit Virus Shows Promise in Multiple Myeloma

A virus that exclusively infects rabbits was used to treat multiple myeloma (MM) in preclinical studies, eliminating most of the malignant cells and eliciting a strong immune response.
 
MM is a difficult to treat disease that is the second most common type of blood cancer. Because of this, scientists are working to develop new treatment strategies.
 
In a study published in Molecular Therapy – Oncolytics, investigators used a novel approach to treat MM with the use of viral oncolytics that target and kill cancer cells.
 
Most patients with MM experience disease relapse because of reinfusion of cancerous cells during stem cell transplantation or expansion of drug-resistant disease after chemotherapy.
 
“What I though was really interesting here was that we could actually get rid of the disease and it didn’t appear to ever come back,” said author Eric C. Bartee, PhD.
 
Myxoma virus (MYXV) is a virus that exclusively infects rabbits. For the past several years, Bartee has been using MYXV to treat MM in cell culture. However, prior work shows that MYXV has the ability to kill human MM cells.
 
Stem cell transplants are commonly used to treat MM, but patients will often relapse from residual cancer cells within the transplant sample, according to the study. However, Bartee demonstrated that treatment with MYXV was successful in eradicating the cancerous cells in the patients’ stem cell samples prior to re-engraftment, which resulted in the prevention of relapse.
 
In the current study, the investigators sought to determine whether treatment with MYXV also had benefit on MM outside the context of transplantation.
 
Using a preclinical mouse model, the results of the study showed that systemic treatment with MYXV reduced tumor burden and led to a modest decrease in disease progression in 66% of mice. Furthermore, complete eradiation of the disease with no evidence of relapse was achieved in 25% of mice.
 
It was hypothesized that eradication of the disease was caused by the host’s immune system, however, an investigation of the bone marrow showed that it was unaffected by treatment with MYXV.
 
The findings suggest that the immune system remained intact and could fight off the cancer cells. Treatment with MYXV led to an increase in CD8+ T cells within the bone marrow compartment, indicating strong antitumor response.
 
Although the findings show promise, there are several barriers that need to be overcome before the novel treatment can become available in the clinic. According to the authors, a significant barrier is the large-scale production of the clinical-grade virus. Furthermore, demonstrating a high response rate can be difficult when moving from preclinical studies in mice to clinical trials in humans.
 
“I think the major next question is ‘How do you get that response rate from 25% to 50% to 80% to 100%?” Bartee said. “How do you define the patient in which it works?”
 
The authors noted that a unique advantage of using MYXV to treat MM is that the response rate observed in the study is not mediated by the virus, but rather the patient’s own immune system. Additionally, it is extremely challenging for MM to develop resistance to killing by MYXV.
 
“I think what our findings, and oncolytics in general, really highlight is that some of these non-traditional therapies can really offer the benefit of complete disease eradication,” Bartee said. “You’re not just moving the curve to the right a little bit; you’re bending the survival curve up. And you’re really fundamentally changing how you can look at cancer treatment.”
 


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