The word revolution is overused and done to death. But in the case of medicine, we are in the midst of one. Here are three stories just out this week. It’s possibly none of these will end up being useful clinically, but the sheer volume of results like these mean that sooner or later getting a diagnoses of cancer will mean something very different. It’s time for good news stories. Let’s redirect the gravy train of pointless climate and renewables research. (Sell the ABC and use the money to double our medical research budget. How many lives might we change?*)
These are not instant miracles, but potential ones. The bladder cancer drug ultimately helped about a quarter of all patients. It was a small trial. Two patients of 68 appeared to reach the holy grail: to be tested free of cancer (though it doesn’t mean they are). The second news report talks about a small study targeting a similar mechanism to stop melanoma that only helps about 30% of patients — the study successfully predicted which ones. In both cases the idea is to stop the cancer from hiding from the immune system. Some cancer cells produce molecules called PD-1 or PD-L1 (I don’t know if they are related) to trick the immune system into leaving them alone. The powerful thing about this is the offer of the holy grail for more people: if the immune system recognizes cancer cells as dangerous, even some late stage disseminated cancers could be cleared in a few months and with few of the side effects of the poisonous chemotherapy drugs. Our cellular soldiers can seek out and destroy the problem cells.
The third news story is an early stage “proof of concept” study. It shows that we can already identify cancer markers to an individual cancer (in mice) and make a vaccine to train the immune system to find it. It’s risky — if we vaccinate people against a marker which is also present on healthy cells we unleash an autoimmune disease. Theoretically with DNA tests we should be able to isolate specific tumor mutations that do not appear in healthy cells. It’s a question of cost. But cancer treatment is currently very expensive and costs of DNA analysis and vaccine creation have fallen dramatically in the last 20 years. Sooner or later this will probably be realistic — perhaps as the last resort for people with rarer cancers that don’t respond to other treatments, or who knows?
Scientists from Queen Mary University of London have made a breakthrough in developing a new therapy for advanced bladder cancer — for which there have been no major treatment advances in the past 30 years.
Published today in Nature, the study examined an antibody (MPDL3280A) which blocks a protein (PD-L1) thought to help cancer cells evade immune detection.
In a phase one, multi-centre international clinical trial, 68 patients with advanced bladder cancer (who had failed all other standard treatments such as chemotherapy) received MPDL3280A, a cancer immunotherapy medicine being developed by Roche. In addition, patients were all tested for the protein PD-L1 and around 30 were identified as having PD-L1 positive tumours.
After six weeks of treatment, 43 per cent of PD-L1-positive patients found their tumour had shrunk. This rose to 52 per cent after 12 weeks of follow up. In two of these patients (7 per cent) radiological imaging found no evidence of the cancer at all following the treatment. Among PD-L1 negative patients, 11 percent responded positively to treatment too
CLA researchers have pioneered a new methodology to predict why some patients battling advanced melanoma respond well or not at all to the new breakthrough drug pembrolizumab (Keytruda).
A protein known as PD-1 puts the immune system’s brakes on, preventing T cells from attacking cancer cells. Pembrolizumab removes the brake lines, freeing up the immune system to kill cancer cells.
“We’ve had amazing clinical success treating patients battling advanced melanoma with pembrolizumab. The challenge is that it only works in approximately 30 percent of patients with melanoma,” said Tumeh, lead author of the study and assistant professor of dermatology. “To address this challenge, we developed an approach that can select for patients that are likely to respond to this therapeutic class.”
In the near future, physicians may treat some cancer patients with personalized vaccines that spur their immune systems to attack malignant tumors. New research led by scientists at Washington University School of Medicine in St. Louis has brought the approach one step closer to reality.
Scientists at Washington University already are evaluating personalized cancer vaccines in patients with metastatic melanoma in a clinical trial led by Gerald Linette, MD, PhD, and Beatriz Carreno, PhD at Siteman Cancer Center. The researchers also are working to use the vaccines against breast, brain, lung, and head and neck cancers, and additional trials are anticipated in the next year or two.
In the new study, which appears Nov. 27 in an issue of Nature focused on cancer and the immune system, scientists tested investigational vaccines in computer simulations, cell cultures and animal models. The results showed that the vaccines could enable the immune system to destroy or drive into remission a significant number of tumors. For example, the vaccines cured nearly 90 percent of mice with an advanced form of muscle cancer.
Creating a personalized vaccine begins with samples of DNA from a patient’s tumor and normal tissue. Researchers sequence the DNA to identify mutant cancer genes that make versions of proteins found only in the tumor cells. Then they analyze those proteins to determine which are most likely to be recognized and attacked by T cells. Portions of these proteins are incorporated into a vaccine to be given to a patient.
*I know true libertarians will say “sell the ABC” and give back the taxes — fair point. I’m being provocative. If the government stopped public broadcasting, and stopped funding medical research too while cutting taxes, we know some funds would be willingly philanthropically donated to medical research. Would this be as much, maybe not, would it be better directed, probably yes. Would research advance even faster — it might. But ultimately I want all three kinds of medical research competing — public funded, corporate profit seeking, and private philanthropy.