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Can the


IMMUNE SYSTEM cure Cancer?

owever much or little you may know about the immune system, there is one thing we can agree on: it’s rather handy during flu season and the winter coldsnap. Recent research has made headlines by showing that our immune system does a lot more than fight the common cold, and that it could be the new saviour in cancer treatment. From a girl with leukaemia at Great Ormond Street Hospital to Jimmy Carter, immunotherapy has been the basis for innovative cancer therapies. But this is no recent development. The relationship between cancer and immunotherapy spans a century. In the 1980s, William Coley, an American surgeon, saw that the tumours of patients with bone cancer spontaneously disappeared after infection. So excited was he by this groundbreaking prospect, he coined the term “Coley’s toxins”, a vaccination consisting of dead bacteria to be injected into cancer patients in the hope of eliminating their tumours. The theory made sense but the results did not live up its promise. Cancer immunotherapy was on the backburner for many years as scientists failed to understand the process of immune regulation. How the immune system distinguished between self and non-self cells was puzzling. Tumours are nasty versions of our own body cells but cleverly avoid immune detection and clearance. For a while, scientists did not understand how cancer cells were seemingly invisible to immune surveillance and the field of cancer immunotherapy existed in a period of limbo. This was until Professor James Allison, formerly of University of California Berkeley and also known as the “Texas T-Cell Mechanic”, identified the T-cell’s immune braking system.

a cancer therapy drug using the checkpoint blockade. Ipilimuab was the first drug of this kind and was used in treating patients with skin cancer. This particular drug works by switching off the inhibitory CTLA-4 signals and allowing T-cells to kill cancer cells. New and improved versions of this drug have since been developed such as pembrolizumab, which was used to treat Jimmy Carter’s melanoma. Research in this area is also at the forefront much closer to home. Sergio Quezada of UCL Cancer Institute and his research team have also focused on a similar molecule to CTLA-4 called PD-1. Tumours express PDL1 surface markers which binds to PD-1 on T-cells to shut down their killing activity. Antibodies, Y-shaped molecules with a complementary shape to PD-L1, were made which blocked these interactions to kill tumour cells. However, a potential side effect of this treatment is autoimmunity where the immune system attacks healthy cells as this mechanism unleashes the brakes of immune regulation. According to review in the journal Science, immune checkpoint therapy currently only offers an overall response rate of 37-38 per cent in patients with advanced skin cancer in a large clinical trial. Sergio Quezada spoke about the future of his research to UCL News: “There has been very exciting progress in this field in recent years but we still need to figure out why some patients respond extremely well to these new therapies whilst others don’t, why these therapies lead to side effects in some patients and not in others and most importantly how to combine them in order to maximise efficacy and reduce toxicities.”

T-cells are a type of immune cell which can destroy infected and cancerous cells. This mechanism of immune braking is called the checkpoint blockade. Cancer cells take advantage of the checkpoint blockade and prevent T-cells from activating these cells as dangerous and destroying them.

However, this is not the only exciting area of cancer immunotherapy. The capability of T-cells extends much further, as T-cells can be engineered in the lab to recognise and destroy cancer cells. Dr Martin Pule, a clinical haematologist at UCL Cancer Institute explained the research goals of Autolus, a biopharmaceutical company spun out of the university to UCL News:

Scientists used this knowledge to conceive

“The key will be to remain at the cut-

ting-edge of T-cell engineering to create a new generation of programmed T-cells acting as autonomous agents to kill tumour cells. What we’ve seen so far in the CAR T-cell field is only the beginning.” T-cell engineering takes T-cells from a patient’s blood and then grows them in the laboratory. These T-cells are reprogrammed so they selectively recognise and destroy cancer cells by introducing a protein called chimeric antigen receptor (CAR). The modified cells are reinfused back into the patient blood where they can circulate through the body and track down cancer cells for destruction. This particular therapy gave encouraging results in a clinical trial of adult patients with leukaemia. These patients had stopped responding to other types of treatments and the disease becomes increasingly harder to treat to the point where most patients die within a couple of months. However, this treatment allowed a subset of patients to remain leukaemia free for over a year. Michel Sadelain, of Memorial Sloan Kettering’s Centre for Cell Engineering, said to The Scientist about these findings: “[Immunotherapy] represents a radical departure from all forms of medicine in existence until now.” Though the results of this therapy are promising, it is still premature to tout immunotherapy as a miracle cure. Cancer is unlike diseases such as influenza or a bacterial infection, where we know when these diseases are cured as microbes are removed from the body. It is difficult to say someone is completely cancer free as cancer cells may still remain undetected in the body, and doctors refer to this period as in remission. But the advantage of cancer immunotherapy over traditional chemotherapy or radiotherapy is that the immune system is able to retain a memory of all the bugs and cancers it encounters. This means it is ready to launch a more powerful and faster response the second time round. There is much promise about the hope of this field and it certainly is an exciting time for cancer immunologists.

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Profile for Pi Media, UCLU

Pi Magazine, Issue 713 - Re:Generation  

Our third issue of 2015-16 explores our generation of millennial, and our collective identity. Why is our generation the way it is - what ex...

Pi Magazine, Issue 713 - Re:Generation  

Our third issue of 2015-16 explores our generation of millennial, and our collective identity. Why is our generation the way it is - what ex...