In 2013, the prestigious Science magazine nominated cancer immunotherapy as their ‘breakthrough of the year’. This came after positive results from clinical trials in skin cancer and leukemia patients showed its potential as a completely new way to treat cancer. One of the intriguing things about it is that there are many approaches scientists can take to harness the immune system’s power. Sophie Lutter investigates and asks if immunotherapy has a future as a way of treating prostate cancer.
So what’s the difference between immunotherapy and more traditional cancer treatments? Well, the short answer is this: immunotherapy treatments aren’t directed at the cancer itself. Instead, they’re aimed at the body’s own immune system, and are generally designed to ‘boost’ this squad of defensive cells, to help them recognise and zap cancer cells, while leaving healthy cells alone.
But it’s pretty clear by now that cancer isn’t a ‘one size fits all’ disease. What’s a promising line of enquiry in one cancer type might be a complete non-starter in another, which begs the question: might immunotherapy lead to a win for men with prostate cancer? So far, that looks possible.
We know that there are a number of different types of immune cells inside prostate tumours. There’s also evidence that the more immune cells move into the tumour area, the better men do. And we know that high levels of a different type of cell that blocks the immune response (regulatory T cells) are associated with more dangerous prostate cancers.
It’s not all plain sailing, unfortunately. Cancers are notoriously good at sneaking past the body’s usual defences. And they’re not afraid to take on the immune system. In fact, prostate cancer cells have a number of strategies to beat the immune defence. Firstly they can disguise themselves by reducing how much they display proteins that mark them as targets for the immune cells. They can simply attack and kill immune cells. And they can secrete substances and recruit regulatory T cells to block the body’s immune response.
So any prostate cancer immunotherapies have some obstacles to overcome. But this hasn’t put researchers off, and there are a number of potential new treatments in the pipeline.
Provenge was the first prostate cancer immunotherapy to be licensed for sale in the UK. It’s also known as sipuleucel-T.
How it works: In this treatment, doctors take immune cells from the patient and incubate them outside the body with a fusion protein, which is made by sticking two different proteins together. One of these is called PAP, which is found on prostate cells, and in particularly high levels on cancer cells. The other is a protein called GM-CSF.
When mixed with the patient’s extracted immune cells GM-CSF can stimulate them to respond to PAP. And once these hyper-responsive immune cells are injected back into the patient, they start attacking PAP-expressing cancer cells, including prostate cancer cells.
The results: Perhaps not surprisingly, Provenge is extremely expensive, and NICE (the National Institute for Health and Care Excellence) couldn’t tell from the evidence the pharmaceutical company gave them whether it worked better than other available treatments for advanced prostate cancer. Overall, the price was too high for the benefits it showed, so NICE couldn’t recommend it for routine use on the NHS.
Provenge isn’t necessarily the first and last word in prostate cancer immunotherapies though.
Ipilimumab is another immunotherapy treatment that has achieved impressive results with advanced melanoma (a type of skin cancer). It works differently to Provenge.
How it works: We talked earlier about how a type of cell called regulatory T cells can stop the immune system from attacking cancer cells. They do this with a protein that blocks the immune cells’ activity. Ipilimumab works by counter-blocking this, which gives the immune cells free rein to work their magic on the cancer cells.
The results: A phase three clinical trial of ipilimumab had mixed results. It took longer for men’s prostate cancer to start growing again if they’d received ipilimumab. But overall, men taking ipilimumab didn’t live longer than those who hadn’t taken it
But this isn’t necessarily the end of the line for ipilimumab in prostate cancer. Not all prostate cancers are the same, and not all men with prostate cancer respond well to the same treatments. The trial did suggest that ipilimumab may work better in certain sub-groups of men with prostate cancer, which is likely to be investigated in future trials.
How it works: Prostvac-VF is another type of immunotherapy. This time, the treatment works by tricking the immune system into thinking it’s a virus, which immune cells are programmed to respond to. The scientists who invented it also inserted the PSA gene into the virus. So when it’s injected into the patient, the virus starts to produce PSA. This tricks the immune system into killing anything producing PSA. Because prostate cancer cells produce so much PSA, the immune cells attack them.
The results: Prostvac-VF has so far been tested in phase two clinical trials, where it had some promising results. Although it didn’t make a difference to the length of time it took for men’s prostate cancer to start growing again, overall, men given Prostvac-VF lived longer than men who didn’t have the treatment.
At the moment, Prostvac-VF is still going through phase three clinical trials, so we’ll have to wait a bit longer to find out how well this treatment works in a larger group of men.
How it works: GVAX is different again. It’s a whole-cell vaccine. This means it’s made from cancer cells which have been exposed to high levels of radiation so that they’re not dangerous anymore. The cells have also been modified to express high levels of a protein we mentioned above called GM-CSF, which stimulates the immune system to attack.
The reason cancer cells are used is because they produce the same proteins as the original prostate cancer. So the GM-CSF in the vaccine stimulates the immune cells to specifically attack cancer cells expressing these proteins. Hence they will begin to attack prostate cancer cells as well.
The results: Unfortunately, GVAX didn’t do well in two phase three clinical trials, which were stopped early. It may still be useful in combination with other treatments though, but we won’t be sure about this until some more tests have been done.
Immunotherapies are certainly not a dead end when it comes to prostate cancer treatment. We’ve just talked about a number of therapies that have already been tested in different stages of clinical trials. And some of them are looking promising – at least in specific groups of men. The next step is to see whether these immunotherapies work even better when combined either with existing treatments or each other. They also need to be tested when given before or after existing treatments. Some of these trials are happening at the moment, and we’ll certainly be keeping an eye out for the results.