Vaccines, along with antibiotics, are the superstars of modern medicine. It’s possible that basic inoculations started in Egypt and China in the 10th century, but the West first heard reports of these practises only in 1700. Scientists reported wondrous tales of Chinese physicians infecting their patients with smallpox. The reaction was predictable – who would willingly infect themselves with a deadly virus? It took almost two hundred years for Western medicine to start using vaccines, and they are today mainstream, with some truly amazing achievements – such as the elimination of smallpox from the surface of the Earth.
The fundamental concept of vaccination hasn’t changed: our immune system is designed to remember every infection it has ever faced, so we train it to fight potentially deadly diseases – if we ever face the real thing, our body remembers the previous infection and jumps to action. The days of injecting live smallpox in your bloodstream are mostly over, however. Most vaccines nowadays inject either a weakened bacterium or virus, or just a molecule called antigen which is like a microorganism’s identity card – either way your immune T-cells, which are largely responsible for killing microorganisms, will retain the mugshots and be ready to attack.
A quick side-note on the vaccine-induced autism hysteria – shoddy science pretended to demonstrate that vaccines led to the possibility of children developing autism. Though this claim has been thoroughly debunked, high profile celebrity endorsements and suspicion in expert opinions means the damaging myth self-perpetuates. Granted, not everything about vaccines is completely understood, but rest assured, there is no evidence whatsoever that vaccines lead to autism.
Perhaps because fighting a bacteria and a cancer isn’t as different as one might think (in both cases, the fundamentals of theory of evolution means you are fighting a multi-headed hydra that is constantly adapting to whatever you throw at it), the idea of creating a cancer vaccine has been kicking around for some time. Historically, the main issue has been trying to find some molecules present on the surface of cancer cells which our immune T-cells could recognize – without also ‘recognizing’ the same molecules on the surface of healthy cells and killing those, too. A couple of recent letters to Nature demonstrates the first proof-of-concept in humans by using cancer vaccines in clinical trials. The advent of powerful genomic technologies is the main reason why studies have now begun taking off: in a healthy patient, most of the body’s cells will have a uniform genome, but in a cancer, the cells go haywire, multiply at breakneck speed and accumulate genomic mutations which neighbouring healthy cells don’t have. Being able to read the whole genome and identify the mutations that cancer cells accumulate (but healthy cells not) is crucial to cancer vaccines.
In a recent study, the team read the patients’ cancerous genome, picked out a few heavily mutated genes (not otherwise present in the healthy genome of the same patient), then used a second genomic technique to make sure the genes were turned on. It’s essential the genes used are turned on, as they would otherwise not produce the molecule they encode – which in turn would therefore not be present in the cell or on the cell’s surface. The team hoped that the molecules produced by the mutated genes would be different enough from the healthy version that the patients’ immune systems would be able to tell the difference. Using a nifty piece of predictive algorithm to pick out targets that were most likely to trip the immune cells, all the team then had to do was synthesize the mutated pieces of protein (along with some adjuvants to increase the chances of getting a reaction from the immune system).
The patients, suffering from high-risk skin cancer, were then injected with the vaccine and monitored closely. The first, happy, conclusion, was the absence of adverse side-effects, which is where most cancer therapies fail to pass the test. Interestingly, the team found that a significant amount of T-cells were now triggered by the mutated proteins (and thus by the tumour cells themselves), and remained largely unfased by the healthy versions.
A recently published second study published takes a somewhat different tack. Instead of injecting patients with mutated proteins, the team injected patients with RNA (a molecule not dissimilar from DNA – RNA contains the code necessary to produce a molecule, as DNA would, and when injected in a patient leads to the production of the aforementioned molecule). The main reason for using RNA instead of DNA is a decreased risk of the injected foreign piece of code messing up healthy cells. The rest of the study design is similar, the idea being that the molcule produced will trigger the immune system, and help T-cells recognize mutated molecules on the surface of cancer cells (while, again, leaving healthy ones intact). The vaccine was tested on 13 patients. The researchers’ results were by and large the same as the first study, namely that the vaccine is safe, and that the patients’ immune cells react to the mutated molecules and start killing off cancerous cells which carry the mutated molecules. Unfortunately, one of the thirteen tumours mounted defences and stopped expressing the proteins that T-cells were hunting, thus evading the immune system (this is known as resistance and is a eternal issue with all cancer therapies). Cumulatively, the 13 patients experienced 3 major relapses of the cancer while under the vaccination protocol, against nearly 30 before the vaccination – indicating that the vaccine was keeping the cancer at bay by encouraging the patients’ immune systems to kill off the tumour cells.
The next logical step will be to test this vaccine against the current gold standard, to see whether a large cohort of patients would profit from such a therapy. This could lead to the advent of personalized therapy, whereby each patient has a custom-made vaccine (since most patients would be expected to have different, though overlapping, mutations that could be sued to trigger their immune system). The issue of resistance will also have to be monitored, as cancers are liable to evolve in a way that makes them resistant to the host’s immune system. On the whole though, there is real hope that a cancer vaccine would lead to a new type of therapy, whereby instead of drugging cancer patient with toxic chemicals and drugs, one could simply prod their own bodies into fighting the scourge.