Entries Published On May, 2017
PrimeVax is a pre-clinical biotech company who has developed a one-time one-week cancer treatment for late stage, non-responding patients using wild type dengue virus and autologous dendritic cells. They expect to enter their first clinical trial in 2017.
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The idea of harnessing the power of the immune system to battle cancerous tumors is not new. A recent BBC article, Cancer: The Mysterious Miracle Cases Inspiring Doctors, discusses one of the strategies that PrimeVax, an angelMD company, is taking.
The BBC article references a case study of William Coley, who famously observed a patient with a large tumor in his neck experience spontaneous remission after catching a nasty skin infection. He tested the principle on a small number of other patients, and found that deliberately infecting them with bacteria or other toxins destroyed otherwise inoperable tumors.
Indeed, recent evidence makes a compelling case that infection can be the key to stimulating spontaneous remission. For instance, per the BBC article,
Rashidi and Fisher’s study found that 90% of the patients recovering from leukaemia had suffered another illness such as pneumonia shortly before the cancer disappeared. Other papers have noted tumours vanishing after diphtheria, gonorrhoea, hepatitis, influenza, malaria, measles, smallpox and syphilis. What doesn’t kill you really can make you stronger in these strange circumstances.
The article goes on to point out that the microbes themselves aren’t directly responsible for the healing – the infection is thought to trigger an immune response that affects the tumor.
Further excerpts from the BBC article are below:
It’s not the microbes, per se, that bring about the healing; rather, the infection is thought to trigger an immune response that is inhospitable to the tumour. The heat of the fever, for instance, may itself render the tumour cells more vulnerable, and trigger cell suicide. Or perhaps it’s significant that when we are fighting bacteria or viruses, our blood is awash with inflammatory molecules that are a call to arms for the body’s macrophages, turning these immune cells into warriors that kill and engulf microbes – and potentially the cancer too. “I think the infection changes the innate immune cells from helping the tumours to killing them,” says Henrik Schmidt at Aarhus University Hospital in Denmark. That, in turn, may also stimulate other parts of the immune system – such as our dendritic cells and T-cells – to learn to recognise the tumorous cells, so that they can attack the cancer again should it return.
Schmidt thinks that understanding the process of spontaneous remission is vital, since it could help refine the emerging class of “immunotherapies” that hijack our natural defences to combat cancer. In one treatment, for instance, doctors inject some cancer patients with inflammatory “cytokines” in order to kick the immune system into action. The side effects – such as high fever and flu-like symptoms – are typically treated with drugs like paracetamol, to improve the patient’s comfort.
But given that the fever itself may trigger remission, Schmidt suspected that the paracetamol might sap the treatment’s potency. Sure enough, he has found that more than twice as many patients – 25% versus 10% – survive past the two-year follow-up, if they were instead left to weather the fever.
There could be many other simple but powerful steps to improve cancer treatment inspired by these insights. One man experienced spontaneous remission after a tetanus and diphtheria vaccination, for instance – perhaps because vaccines also act as a call to arms for the immune system. Along these lines, Rashidi points out that a receiving standard vaccine booster – such as the BCG jab against tuberculosis – seems to reduce the chance of melanoma relapse after chemotherapy.
Catching a Cure
Others are considering a far more radical line of attack. For instance, one approach aims to deliberately infect cancer patients with a tropical disease.
The technique, developed by American start-up PrimeVax, involves a two-pronged approach. It would begin by taking a sample of the tumour, and collecting dendritic cells from the patient’s blood. These cells help coordinate the immune system’s response to a threat, and by exposing them to the tumour in the lab, it is possible to programme them to recognise the cancerous cells. Meanwhile, the patient is given a dose of dengue fever, a disease normally carried by mosquitoes, before they are injected with the newly trained dendritic cells.
Under the supervision of doctors in a hospital, the patient would begin to develop a 40.5C fever, combined with the widespread release of inflammatory molecules – putting the rest of the immune system on red alert. Where the tumour was once able to lurk under the radar, it should now become a prime target for an intense attack from the immune cells, led by the programmed dendritic cells. “Dengue fever crashes and regroups the immune system, so that it is reset to kill tumour cells,” says Bruce Lyday at PrimeVax
Infecting vulnerable patients with a tropical illness may sound foolhardy, but dengue fever is less likely to kill the average adult than the common cold – making it the safest choice of infection. Importantly, once the fever has subsided, the programmed immune cells will remain on the lookout for the tumour, should it reappear. “Cancer is a moving target. Most therapies attack from just one side – but we’re trying to put it in a lose-lose situation, now and in the future,” says Lyday.
No one could fault the ambition behind this kind of therapy. “Our mission is to replicate spontaneous remission in as standardised way as possible,” says Lyday’s colleague Tony Chen. Even so, they are keen to emphasise that their idea is still at a very early stage of development – and they cannot know how it will play out until they begin a clinical trial. The first tests, they hope, will begin with advanced melanoma patients, perhaps by the end of the year.
Clearly, caution is necessary. As Irvine points out: “Spontaneous remission is a little clue in a big complicated jigsaw.” But if – and that is a massive if – they succeed, the implications would be staggering. A rapid, relatively painless recovery from cancer is now considered a miracle. The dream is that it might just become the norm.”
With the advent of immune-oncologic agents, we are entering a brave, new era of cancer therapeutics. Several companies already have seen early clinical and commercial success with treatments that target a facet of the immune-modulated innate response to tumors. Thus, there is no doubt that the future of anti-cancer therapy lies in harnessing the power of the immune system. PrimeVax is poised to enter this exciting market with a unique approach that is poised to play an important role in treating cancer.
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