This is another example of why I’m so passionate about getting research money out of dead-end efforts to change the weather and into medical research. The extraordinary news broke last week that the Mayo Clinic had used a genetically modified virus to
cure treat one woman of metastasized and widely spread cancer – specifically myeloma. There are a lot of caveats, this research is quite risky, and it doesn’t apply to most people or most cancers, it is a proof of principle.
The potential for transformative medical breakthroughs is spectacular right now. Medicine is, after all, just an information game. The information is expensive but the material resources are dirt cheap — all the answers to the holy grail of the fountain of health are found in rearrangements of common elements — like the kind found in the dirt of a pot-plant. For the first time humanity has the tools to hunt and hammer out the information. If people knew what glittering marvels were within reach, they surely would want to channel our best and brightest and all our spare resources.
The main caveat here (a pretty big one) is that the trial had only two people, and it didn’t help the other person very much. Another caveat is that both people didn’t have antibodies to the measles virus used — and most people would. Other problems with viral treatments are that our immune systems attack the viruses, sometimes before the viruses can act, sometimes the viruses just wash away from the site, then there’s the risk that viruses can mutate. Live viruses can also potentially set up chronic low grade infections in unexpected places. Indeed we are playing with fire. Jesse Gelsinger was 18 when he took part in a medical trial in 1999, and was injected with a “safe” viral vector, he suffered a massive immune response and major organ failure leading to his very premature death four days later. This shocked the research world.
On the other hand, cancer is one of the top two killers in the Western World. The weapons we throw at it are awfully blunt. But theoretically even late stage cancer could be cleared within weeks from a body if the immune system (or a virus) could target just the cancer cells.
I find the possibilities tantalizing. It’s why I studied molecular biology and genetic engineering. One day people will visit their doctor to hear they have aggressive disseminated bowel cancer, say, but they will only need to take an injection and spend a week in hospital with ongoing monitoring. Why aren’t we moving mountains to make this happen?
From the Washington Post ( hyped and lacking in details that I would like to see):
She had been through chemotherapy treatments and two stem cell transplants. But it wasn’t enough. Soon, scans showed she had tumors growing all over her body.
Five minutes into the hour-long process, Erholtz got a terrible headache. Two hours later, she started shaking and vomiting. Her temperature hit 105 degrees… Over the next several weeks, the tumor on her forehead disappeared completely and, over time, the other tumors in her body did, too.
From the Mayo Clinic: Taming Measles Virus to Create an Effective Cancer Therapeutic
May 13, 2014: In this issue of Mayo Clinic Proceedings, Russell et al4 from Mayo Clinic report, for the first time, the use of a cytolytic replicating MV to completely eliminate widespread tumors in a patient with advanced incurable myeloma.
This is not a cure yet
The Cancer Research UK blog tells us that that Stacy Erholtz forehead tumor disappeared for nine months, which they describe as “an incredible outcome” but it has returned and is being managed by radiotherapy. Which all seems rather important, and ought to be mentioned in all the stories you would think. For those who want more info, the Cancer Research UK post seems to be the most balanced and informed.
Why the measles virus was chosen:
The choice of MV as a therapeutic agent for myeloma was not happenstance, but rather the result of several years of thoughtful biological experimentation and rational virus engineering. Russell et al recognized several features of myeloma that would complement the life cycle of MV. Myeloma is the second most common hematologic malignancy in North America, and although treatable, it is essentially an incurable disease with a 5-year survival rate of less than 40%. A hallmark of the disease is the seeding of malignant plasma cells throughout the bone marrow, ultimately impairing the production of normal blood cells and creating lesions in the bone (see Figure 2, A in Russell et al4).
During natural infections, MV gains access to the bone marrow through infection of the reticuloendothelial system, thus making it an ideal agent to attack myeloma cells exactly where they hide. CD46, a cell surface antigen, is the receptor for MV and is highly overexpressed on the surface of myeloma cells, making them prime targets of infection.5 Measles virus is rapidly neutralized and inactivated in the bloodstream by antibodies that arise following vaccination or natural infections.6 Neutralizing antibodies provide a safety shield against MV infections for most North Americans. In many myeloma patients, however, neutralizing antibodies directed against MV are at very low levels or absent because both the disease and the current therapies used to treat it are immunosuppressive.
Though this study only has a trial of two patients there are many other studies going on with other viruses, other clinics and other cancers. Here’s one, announced this week.
Herpes-loaded stem cells used to kill brain tumors (in mice)
Harvard Stem Cell Institute (HSCI) scientists at Massachusetts General Hospital have a potential solution for how to more effectively kill tumor cells using cancer-killing viruses. The investigators report that trapping virus-loaded stem cells in a gel and applying them to tumors significantly improved survival in mice with glioblastoma multiforme, the most common brain tumor in human adults and also the most difficult to treat.
The work, led by Khalid Shah, MS, PhD, an HSCI Principal Faculty member, is published in the Journal of the National Cancer Institute. Shah heads the Molecular Neurotherapy and Imaging Laboratory at Massachusetts General Hospital.
Cancer-killing or oncolytic viruses have been used in numerous phase 1 and 2 clinical trials for brain tumors but with limited success. In preclinical studies, oncolytic herpes simplex viruses seemed especially promising, as they naturally infect dividing brain cells. However, the therapy hasn’t translated as well for human patients. The problem previous researchers couldn’t overcome was how to keep the herpes viruses at the tumor site long enough to work.
Shah and his team turned to mesenchymal stem cells (MSCs) — a type of stem cell that gives rise to bone marrow tissue — which have been very attractive drug delivery vehicles because they trigger a minimal immune response and can be utilized to carry oncolytic viruses. Shah and his team loaded the herpes virus into human MSCs and injected the cells into glioblastoma tumors developed in mice. Using multiple imaging markers, it was possible to watch the virus as it passed from the stem cells to the first layer of brain tumor cells and subsequently into all of the tumor cells.
Ideally, if we use viruses, I’d like to see a two stage process where the viruses were themselves removed after the treatment. Perhaps we could combine the virus dosage with something that shielded it from the immune system, and after the cancer was cleared we could unshield it and let the immune system mop up the virus too. That might also help with people who were immune to the therapeutic virus to start with.
h/t to Robert who keeps prodding me with the most interesting medical news.
This post is dedicated to Jaymez. We don’t just want a treatment. We want a cure.
Russell, S.J., Federspiel, M.J., Peng, K.-W. et al. Remission of disseminated cancer after systemic oncolytic virotherapy. Mayo Clin Proc. 2014; 89 (XXX-XXX)
Duebgen, M., et. al. Stem cells loaded with multimechanistic oncolytic herpes simplex virus variants for brain tumor therapy. Journal of the National Cancer Institute. June 2014. (Early access May 16, 2014)