New Zealand Science Teacher

Targeting our immune system, not the disease

23/04/2015

KATHERINE ALLEN writes about the emergence of immunotherapy, and the research being done at Wellington’s Malaghan Institute of Medical Research.

Somewhere, sometime in the future, we may look back and wonder when the mainstream use of the term ‘immunotherapy’ first began.

But for now, use of the word and understanding of the concept – targeting our immune system to fight disease, rather than targeting the disease – are yet to become widely established, but awareness of both is certainly growing. 

Over the last century, the components of the immune system have been identified one by one. At the same time, our knowledge about how we can employ our immune cells to battle cancer has also expanded.

Ralph Steinman’s discovery of dendritic cells in 1973 turned the spotlight on these rare white blood cells within the immune system. Making up less than one per cent of our white blood cells, the role of the dendritic cell is to interact and sample the cellular environment, ‘looking for trouble’. 

If they detect foreign bacteria or a virus, the normally unexcitable cells become highly excited. They grow in size, enter the lymphatic system, travel to the lymph nodes and ‘wake up’ an immune response – the B and T cells. Dendritic cells are removed from blood transfusions because of this very quality. A dendritic cell from donated blood would automatically set off an unwanted response in the recipient, but in our own bodies they are less likely to notice something amiss; cells going haywire, or cancer.

Researchers found they could ‘educate’ a dendritic cell in a test tube to notice a tumour cell, and the path to an educative or therapeutic vaccine for cancer was born. There are several drawbacks to the first generation of cancer vaccines though. Firstly, the bespoke nature of the process means each vaccine is individually prepared and the relative rarity of the dendritic cells means that once the ‘educated’ cells are returned to the patient, the provoked immune response may not be strong enough alone to battle the cancer. 

International investigations simultaneously turned to a complementary avenue: understanding why, and what, holds back a greater immune response. Turning off the molecules on the outside of T cells that keep our immune system in check, and prevent us ‘attacking’ ourselves, has led to ‘checkpoint inhibitors’ being added to the arsenal of cancer treatments.

The Malaghan Institute of Medical Research in Kelburn, Wellington employs these newer immunotherapy treatments in research programmes, while investigating second generation vaccine possibilities; synthetic preparations which need not be made individually, and could in theory be given to anyone with a particular cancer.

Additional to cancer immunotherapy, researchers at the Malaghan Institute are increasingly interested in the role our gut plays in mediating many other diseases; from allergies and asthma, obesity and type 2 diabetes, through to multiple sclerosis and heart disease. Medical research is revisiting the old adage ‘you are what you eat’ through a more contemporary lens as it may be more accurate to say ‘you are what your gut bacteria eat’.

The immunological consequence of our own status as host to the approximately 100 trillion microbes that inhabit our bodies has just begun to be investigated. Bacteria in an average human body number ten times more than human cells, for a total of about 1000 more genes than are present in the human genome.

The genes of the microbial species inhabiting our bodies make up what is called ‘the microbiome’. The Human Microbiome Project was based on an assumption that all humans would share a large ‘core’ of microbial lineages, with a small amount of diversity making each of our microbiota compositions unique. Remarkably, this turned out to not be the case, and striking variability among the most common microbes has been observed. As a result, the connections between the microbiota and immune function are just beginning to be established.

In March, the Malaghan Institute’s gut immunology team leader Dr Liz Forbes-Blom was awarded a $400,000 grant to investigate what are known as functional foods – foods to support the immune system – by the Ministry of Business, Innovation and Employment.

Somewhere in the future, immunotherapy may be the primary therapeutic principle in medical care.

Find out about a unique teacher's event taking place on May 7 at the Malaghan Institute in Wellington. Secondary science teachers welcome.

-          Katherine Allen is communications and marketing manager at Wellington’s Malaghan Institute of Medical Research.