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UK team breach pancreatic cancer’s protective wall to kill cells using immunotherapy

23 December 2013

Researchers from the University of Cambridge have identified how the protective ‘wall’ around cancer tumours functions and how to break it down, enabling the body’s own defences to reach and kill the cancer cells within.

The discovery has led to the development of a possible new method for treating pancreatic cancer by enabling the body’s immune system to attack and kill the tumour cells. 

The method uses a drug which breaks down the protective barrier surrounding pancreatic cancer tumours, enabling cancer-attacking T cells to get through. The drug is used in combination with an antibody that blocks a second target, which boosts  the activity of these T cells.

Initial tests of the combined treatment, led by Professor Douglas Fearon and his team at the University’s Cancer Research UK Cambridge Institute, resulted in almost complete elimination of cancer cells in one week.

The findings mark the first time this has been achieved in any pancreatic cancer model.  In addition to pancreatic cancer, the approach could potentially be used in other types of solid tumour cancers.

Immunotherapy – stimulating the immune system to attack cancer cells – is a promising therapy for several types of solid tumours, but patients with pancreatic cancer have not traditionally responded to this approach, possibly because the human form of the cancer, as in animal models, also creates a protective barrier around itself.

The research team found that this barrier is created by a chemokine protein known as CXCL12, which is produced by a specialised kind of cell, called a carcinoma-associated fibroblast, or CAF. The CXCL12 protein coats the cancer cells acting like a biological shield that keeps T cells away.

The effect of the shield was overcome by using the drug AMD3100, also known as Plerixafor,  to allow the T cells to penetrate the tumour, and was combined with an immunotherapeutic antibody called anti-PD-L1 which boosts the activity of T cells to attack and kill the cancerous cells.

Using this combination approach, the number of cancer cells and the volume of the tumour were greatly diminished – and after one week, the residual tumour was composed only of premalignant cells and inflammatory cells.

Maggie Blanks, CEO of the Pancreatic Cancer Research Fund commented: “Harnessing the power of the immune system to attack tumour cells is a promising field of research, but it’s been disappointing that the progress with other cancers hasn’t been seen with pancreatic cancer.

“What’s exciting about this latest research is that it looks like we’re finally seeing the obstacles to immunotherapy in pancreatic cancer being understood and overcome. These findings go another step towards developing desperately needed new treatments for pancreatic cancer, the most lethal of all cancers.”

The study was reported in the US journal Proceedings of the National Academy of Sciences and was funded through support by GlaxoSmithKline, the Medical Research Council, Addenbrooke’s Charitable Trust, the Ludwig Institute for Cancer Research, the Anthony Cerami and Anne Dunne Foundation for World Health, and Cancer Research UK. 

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