Malignant melanoma is unfortunately one of the cancers on the increase. Our love of sunshine holidays, and using insufficient protection against the sun’s rays can result in one of the deadliest cancers. Estimates suggest that in 2010, 68,000 melanomas will be diagnosed in the USA, resulting in almost 9,000 deaths.

Early diagnosis is critical, allowing removal of the malignant growth. Late-stage identification of the problem means the prognosis is poor. Chemotherapy is the sole treatment on offer and response rates are very low.

Immunocore, based at Milton Park, has recently been granted approval for clinical trials in the UK and USA of its targeted therapeutic, TMCgp100. The trials will be on late-stage melanoma.

Founder and chief scientific officer Dr Bent Jakobsen explained the drug is designed to help the immune system both find the cancer and destroy it.

He said: “Our immune system develops at a very young age and what we have, we have for life.

“It’s possible to modify or strengthen the system on a temporary basis to fight a particular disease, but we can’t alter it permanently.

“Our drug is aimed at boosting the immune cells’ ability to detect the cancer, then harness all the cells to fight it.”

The immune system is a tremendous weapon in combating illness. Because it is unique to each of us, it acts in harmony with our body, minimising the chances of side-effects.

Every day, it will find problems such as abnormal, pre-cancerous cells, and eradicate them. But the system is complex with about 25 million constituent parts, each one dedicated to a different abnormality.

A certain level of pre-cancerous cells have to build up before the body will detect them. If the cells do not reach that level, the cancer can remain hidden. It is called tolerance. If found, the cancer will be attacked only by those cells dedicated to it.

Tmp100 sharpens the cells’ hunting instincts and orders all the body’s immune cells to launch resistance, not a mere handful.

The cells involved in this search and destroy sequence are called T cells. The protein that the immune system utilises to find abnormal cells is called a receptor.

But cancer cells are 99.9 per cent like normal cells — it is only the activities of a few abnormal genes that produce proteins not found in normal cells.

Whole proteins are hard to recognise and, in any case, are contained within a cell. Fortunately, the abnormal proteins break down into what are known as peptide fragments, which sit on the cell’s surface, rather like flags.

Having found the cancer, the tmp100 binds strongly to it, then signals all the immune cells to attack — especially those that respond to viruses.

Tmp100 is part of the company’s ImmTAC technology, a platform that can be used as a base in other areas such as solid cancer tumours, leukaemia and hepatitis C.

Late-stage melanoma was chosen as the first target for a number of reasons. First, it was the disease in which Immunocore’s research showed the greatest success.

Clinical trials are far more justifiable, in that there is little or nothing else that can be done for a patient.

Intervention with the trial at earlier stages might compromise other treatments on offer. Melanomas are tumours visible on the skin’s surface, thus any regression or reduction in a tumour is clearly observed. Plus the immune system is particularly good at resolving skin problems.

Dr Jakobsen said: “It’s a little sad but true that despite all the research, the primary weapon against any cancer is still surgery.

“A melanoma forms on the skin’s surface and it stays treatable while it remains on the surface. Once it penetrates the skin and the blood system, that is when it becomes deadly. We hope that tmm100 will not only regress the cancer, but cure it as well.”

Cancers mutate as they progress and everyone’s cancer is a little different to someone else’s.

Immunocore’s research aims to profile cancers better, and it is possible its drug will be part of a series, or perhaps a cocktail, to effect that total cure.

Given singly, any drug may well reduce a cancer, but not affect some malignant cells. When the cancer returns, the original drug has no effect, so a second or third drug is needed to eradicate all the cells.

The UK clinical trial, already under way, will be a standard test for toxicity and reaction, gradually increasing doses, and will last 12-18 months.

For the USA, it will be an exploratory trial for patients who have no treatment options left.

Melanoma will metastasise just like any other cancer, forming tumours elsewhere in the body. The trial will involve direct injection into just one of the tumours, thus ensuring a high initial drug concentration, and will take six to eight months.

Immunocore’s future plans revolve around five cancer programmes, which will begin while the melanoma trials are still underway.

“We really want to push our technology,” said Dr Jakobsen.

Name: Immunocore Established: 1999 Chief executive: James Noble Number of staff: 45 Annual turnover: Confidential

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