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Vaccine therapy for cancers

30 April 2015

The components of the immune system have been identified step-by-step during the 20th century which has enabled research into how we can employ it to battle cancer to expand in parallel.

Ralph Steinman’s discovery of Dendritic Cells in 1973 turned the spotlight on these rare white blood cells of the immune system. Making up less than 1% of our white blood cells, the DC’s role 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.  DCs are removed from blood transfusions because of this very quality.  A DC from donated blood would automatically set off an unwanted response in the recipient, but in our own bodies they are less like to notice something amiss; cells going haywire, or cancer.

Researchers found they could ‘educate’ a DC 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 DCs means once the ‘educated’ DCs 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’ adding to the arsenal of cancer treatments.

The Malaghan Institute employs these newer immunotherapy treatments in research programmes while investigating second generation vaccine possibilities; synthetic preparations which need not be made individually and can be given to anyone with a particular cancer.  An adjuvant is sometimes administered with the vaccine. Our original adjuvant, alpha-galactosylceramide, derived from a marine sponge, is being trialled with a vaccine in patients with melanoma.  This clinical trial began in July 2013 with forty-six melanoma patients, and while ethical guidelines prevent any discussion of progress, international and local discoveries will inform subsequent trials.