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Friday, 8 June 2012

Immunology and Cancer

Ten years ago the author of a keynote speech on the science of immunology remarked: "The paradox of today's immunology is that tremendous progress in basic science has been matched by only a few clinical applications." At the time, he noted, a journal paper in immunology was being published every 15 minutes but little of this knowledge was translated into useful treatments for patients.
The task of trying to understand what is happening in the immune system reminds me of the Walrus and the Carpenter who wondered whether the shore could be cleared of sand: "if seven maids with seven mops swept for half a year". You could envisage those poor maids, sweeping diligently, only to discover layer beneath layer of sand. So it has been in the biological sciences with layer after layer of complexity being revealed, the deeper the scientists dig. Ten years ago only ten of the immune-based drugs known as monoclonal antibodies were in use. The list has grown rapidly since then and many of them being used to treat various forms of cancer. It has taken an astounding amount of pure research to enable these immune-based treatments to prolong lives. Herceptin is the best known example.
In the world of cancer drug development there are a two main strategies. The traditional one is to try out various chemical compounds until you find one that kills cancer cells without killing, or permanently damaging the patient. The more recent and much more sophisticated method is to pinpoint a particular cancer gene or molecular pathway, and then devise a molecule that will block the gene or disrupt the pathway. Unlike the generic weedkiller approach of chemotherapy the new drugs are very specific. They may have dangerous side effects but they are unlikely to be the ones that traditionally accompany chemotherapy: hair falling out and immune system being seriously impaired.
Some of the underpinning research is done by immunologists who are slowly starting to understand the puzzling interactions between cancers and the immune system. We have known for a long time that some immune cells can destroy cancer cells and in recent years there is increasing understanding about why they might fail to do so and how, sometimes, immune cells are deceived into promoting the spread of cancer. But the processes have to be unpicked, one molecule at a time if they are to be used by medicine.

Research published in this month's New England Journal of Medicine reveals some encouraging results for another antibody-based drug. The interesting thing about this one is that it operates directly on one of the molecular interactions between the immune system and cancer. It does not, as Science Daily implies in its headline "boost" the immune system. Instead it prevents the cancer from using one of the possible ways of defending itself against an immune attack.

The new drug was tested on 296 patients who were suffering from some of the more lethal kinds of cancer - melanoma, lung cancer and so on, who had already had other forms of treatment. The results showed that "approximately one in four to one in five patients" responded in an encouraging way. These results are exciting, given the nature of their diseases. Immunology did indeed make slow beginnings in terms of practical applications, but at last it is starting to produce benefits for patients.
Antonio Coutinho Immunology at the crossroads EMBO Rep. 2002 November; 3(11): 1008–1011.

Suzanne L. Topalian et al. Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in CancerNew England Journal of Medicine, 2012 DOI

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