Boom Or Bust: Why Does Cancer Immunotherapy Have Such Mixed Results?

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Treating cancer by boosting the immune system has been hailed as a major breakthrough in cancer treatment. It may melt away tumours in some patients but it isn't always effective, and can even be dangerous.

 The FDA approved two new immunotherapy drugs in 2015, and over half current cancer trials now involve immunotherapy. The field has the potential to completely change cancer treatment, but it's still early days. 

 Dr. Steven Rosenberg and Linda Taylor, the first patient to be cured with immunotherapy 

It works fantastically well...in some people

In 1984, Dr Stephen Rosenberg from the NCI first attempted a revolutionary new therapy which triggered the host's own immune system to destroy cancer. At the time Linda Taylor was suffering from an advanced metastatic melanoma, an aggressive type of skin cancer. 80 patients failed to respond effectively to the procedure and sadly passed away, but in the 81st, Linda Taylor, it melted away to a total remission. Today the treatment is far kinder and about 20% of patients also experience total remission.  

But it can also kill

Activating the immune system is playing with fire, and the most deadly epidemic in history proves it. The 1918 outbreak of Spanish Flu wiped out 50-100 million people (3-5% of the world's population at the time). It did this by triggering a huge 'cytokine storm' in the healthiest individuals, in which the immune system went into catastrophic overdrive and killed the host. There's a reason why your immune system is often repressed by the body, and diseases like rheumatoid arthritis and diabetes illustrate what damage a rogue immune system can wreak. Your immune system guards you against millions of foes every day, and it has an extremely powerful cocktail of chemicals at its disposal. If this force is directed at your own cells it can turn nasty.

"We have had some treatment-related deaths. That's been true in the field as well as in our own experience"

Getting the right balance

A powerful treatment requires caution, but research is revealing how to activate safely and specifically. The odd cancerous cell appears in young, healthy people, but immune cells generally dispatch them quickly. One way cancer can survive is by tricking and masking its presence,but a promising route in immunotherapy is to remove this cloaking. This tactic is called checkpoint blockade, and applies antibodies to find the tumour and intensify the immune response. This treatment has fewer side effects in skin cancer patients than lung cancer, but only recently have scientists begun to understand the differences. 

The checkpoint blockade approach particularly works on tumours created by environmental stressors like smoke or UV damage, but it often fails against cancers like prostate or pancreatic which are usually caused by a few specific mutations. These are called 'cold' tumours, because they're harder to pick up. 'Hot' tumours are easier to target because they already have damage associated proteins coating them. Another immunotherapy approach involves killing off a few of these cold tumour cells - to release their content and attract immune cells towards them. This approach doesn't work for very long, but researchers are looking for ways to improve it.

Lowering the dose

Treatments like radiation and chemotherapy can also be used to lower immunotherapy doses, and help prime the immune system too. They release triggering proteins by killing a few cancer cells, which then alerts some immune cells of the malignant presence. Lowering the dose helps improve safety, and prevent a dangerous overreaction. This combination approach could eventually become the gold standard of cancer treatment.

Next generation immunotherapy

The newest addition to the field is CAR-T cells, which are genetically engineered 'super' T cells specifically designed to target cancer. Clinical trails using these CAR-T cells have produced remission rates of 90% in a number of advanced blood and lymph cancer types. As the field evolves with advances like CRISPR-Cas9 gene editing and gene therapy improvements, efficiency could be improved even further. 

Read more at Scientific American