A proof-of-principle study has demonstrated that the measles virus can be harnessed to infect and kill cancer cells in patients with multiple myeloma, without harming healthy tissue.
Writing in the Mayo Clinic Proceedings, researchers report clinical data from two patients treated with NIS-expressing measles vaccine (MV-NIS), a recombinant oncolytic measles virus that targets myeloma plasma cells.1
“These patients were not responsive to other therapies and had experienced several recurrences of their disease,” said lead author Stephen Russell, MD, PhD, a hematologist at the Mayo Clinic in Rochester, MN.
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Within 6 weeks after a single intravenous dose of the virus, both patients responded with reductions of bone marrow cancer and myeloma protein. The first patient, a 49-year-old woman, had “a remarkable response,” Dr. Russell said. “A tumor on her forehead regressed completely and the other lesions that were visible on her PET-CT scan disappeared completely. Her bone marrow, which was diffusely infiltrated with myeloma cells, cleared.”
In a video interview Dr. Russell said, “Her remission lasted for 9 months and then she had a local relapse of the tumor on her forehead, which has been treated with local radiotherapy because her bone marrow remained clear and none of her other lesions recurred.”2
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The second patient, a 65-year-old woman, did not respond as well as the first, having only limited improvement in some of her soft-tissue lesions.
MV-NIS is effective against myeloma because it was engineered to target CD46, a complement regulatory protein that is highly expressed on myeloma cells.
MV-NIS was also engineered with a “snitch gene” that that causes them to concentrate radioactive iodine so that their spread in the body can be monitored with single-photon emission computerized tomography imaging.
In the first patient, radioiodine uptake in the plasmacytoma in the frontal bone was increased on day 8 and further increased on day 15, indicating propagation of the MV-NIS infection. No sign of viral spread to surrounding tissue was seen.
Imaging studies of the second patient clearly demonstrated that MV-NIS preferentially targeted tumor cells, with “striking” radioiodine uptake in several plasmacytomas, the authors wrote. However, uptake was diminished at day 15 and no longer detectable at day 28.
Both patients experienced significant toxicity after the infusion, including headache, fever, tachycardia, hypotension, nausea, and vomiting, but these symptoms responded to treatment or resolved spontaneously.
Previous studies have used intratumoral administration of oncolytic viruses to trigger immune-mediated destruction of multiple myeloma cells, but this was the first to demonstrate the efficacy of systemic administration.
“The dream that we locked onto is that maybe it would be possible to give the virus intravenously and to eliminate cancer systemically rather than to give it as an intratumoral therapy,” Dr. Russell said. “This is the first study to establish the feasibility of systemic oncolytic virotherapy for disseminated cancer.”
The two patients reported on in this study were part of a phase 1 dose-determination trial that began with doses 100,000 times lower than those they received.
In an accompanying editorial, John C. Bell, PhD, suggested that the high dose they received established a critical threshold of virus concentration in the blood, allowing the virus to overcome natural immunologic barriers, survive, and spread.3
Dr. Bell pointed out that both patients reported on in this article lacked anti-measles antibodies, which probably played an important role in their response. To treat patients with previous exposure to measles, MV-NIS will have to be modified so that it can be hidden from the patient’s immune system.
References
- Russell SJ, Federspiel MJ, Peng K-W, et al. Remission of disseminated cancer after systemic oncolytic virotherapy. Mayo Clin Proc. 2014 May 12. pii: S0025-6196(14)00332-2. http://www.mayoclinicproceedings.org/article/S0025-6196(14)00332-2/fulltext. Accessed June 23, 2014.
- Russell S. Remission of disseminated cancer after systemic oncolytic virotherapy. https://www.youtube.com/watch?v=FuUAlChGonE. Accessed June 23, 2014.
- Bell JC. Taming measles virus to create an effective cancer therapeutic. Mayo Clin Proc. 2014 May 12. pii: S0025-6196(14)00368-1. http://www.mayoclinicproceedings.org/article/S0025-6196(14)00368-1/fulltext. Accessed June 23, 2014.
