Immunotherapy- A new weapon in our arsenal against cancer

Radiation and Chemotherapy have long been the staple methods of treating cancer; however amplifying our own immune systems yields promising results.

There is an almost perverse satisfaction in the knowledge that cancer has existed almost as long as we have as a species. That unlike climate change, oil spills or the loss of the dodo, this isn’t the result of one of our own misdeeds with the earliest known case of a cancerous tumour apparent in the fossilised jaw bone of an early Pleistocene humanoid. The word cancer itself can be traced back to Hippocrates and the disease is well documented in ancient Egyptian medical texts as an ailment for which “there is no cure”. Except of course- now there are

At last week’s AAAS meeting (American Association for the Advancement of Science), Dr Stanley Riddell of the Fred Hutchinson cancer Research Centre in Seattle announced his team’s work modifying the immune system to recognise certain types of blood cancers. In what Dr Riddell described as “unprecedented”, 93% of a group of 35 patients with terminal Acute Lymphoblastic Leukaemia (ALL) went into remission. Similar results were displayed in over half of patients diagnosed with lymphocyte leukaemia and non-Hodgkin Lymphoma.

The Science

The treatment consists of modifying a set of the patient’s white-blood cells known as T-cells, cellular blood hounds (pun not intended) able to identify the molecular signatures of threats to the body and destroy them. Unfortunately this capability hasn’t found a way around the defences of cancerous cells which have evolved a variety of methods to shield their molecular signatures from our prying immune system. (Cancer Research UK has a number of great articles detailing how this works)

The T-cells are extracted from the patient and a synthetic virus is used to implant them with a new gene that allows them to recognise a molecule called CD19 found on the surface of a number of blood cancers. The modified T-Cells are then allowed to replicate in the lab before being implanted back into the patient. Equipped with their new receptors, the T-cells quickly hone into their targets and destroy them (see my crudely created diagram below).

Screen Shot 2016-02-27 at 15.40.39

Reasons for Pessimism

The results are indeed “extraordinary” as Dr. Riddell put it, with all of the patients in the trial having an initial prognosis of two to five months. However, care should be taken before touting this as the ‘Cure for Cancer’ as certain media outlets have proclaimed. A cancer patient in remission isn’t necessarily rid of the disease as Dr. Riddell went on to mention, “the response is not always durable, some of these patients do relapse”. Until a full scientific paper of the study has been published and scrutinised, we won’t know the exact details of this experiment or its lasting effects.

Collateral Damage

There is also the matter of side effects. The reason the trial was run exclusively with patients in the latest stages of cancer was due to them having exhausted all other options, and unleashing the full force of the immune system can lead to serious repercussions. ALL, Chronic Lymphocyte Leukaemia and non-Hodgkin Lymphoma are all cancers that affect B-cells, another type of white blood cell in the immune system and CD19 is not a molecule exclusive to diseased cells, they are present on all B-cells- cancerous or otherwise. The modified T-cells will destroy their cellular cousins indiscriminately and whilst a patient can survive without B-cells, they will require life-long drug treatment to compensate.

T-cells can do more than just destroy healthy cells however. Once a target molecule has been recognised, T-cells can begin multiplying at an accelerated rate and produce a potent chemical response known as a ‘cytokine storm’. The effects of this proved fatal for two patients in the trial and twenty others suffered from fever, hypotension and neurotoxicity. The more progressive the cancer in the patient the more powerful the reaction it seems.

Transferability

Cancer Research UK has stressed that whilst immunotherapy has proven effective in treating a range of blood cancers, a number of treatments already exist for these. They argue that time and money would be better spent targeting ‘solid’ cancerous tumours. Tumours are equipped with a number of defences against our immune system and researchers have yet to find a way around this.

Plenty of reasons for Optimism

The amount of work still remaining to take this treatment from the lab to the clinic shouldn’t overshadow the promise immunotherapy holds. A separate study by the San Rafaelle University in Milan has looked into so called ‘memory T-cells’, cells that remember how to identify blood cancers and then persist in the blood stream for up to 14 years offering protection from reoccurrence or reinfection.

Work is also being undertaken to minimise friendly fire by overenthusiastic T-cells. Cancer Research Uk has looked into equipping T-cells with a kill-switch to shut them down if the effects get out of hand (think the droid army at the end of the Phantom Menace). These are currently in early clinical trials at University College of London and Great Ormond Street Hospital. Similarly, research is underway to equip T-cells with the means to bypass the defences of solid tumours and also to adapt the technique to treat HIV, immune deficiencies and other autoimmune diseases.

So whilst there is still some time before T-Cell modification therapy makes its way out of the labs and into general clinics, it seems that immunotherapy could indeed one day join the ranks of our growing arsenal against our age old enemy. I for one hope it’s sooner rather than later.

-Written by Areeb Siddiqui. Images are either royalty free or created by myself. There is no one to blame but myself for how bad they may or may not be.
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