Personalised skin cancer vaccine

08 July 2017
Posted by Chris Smith.

Scientists in the US and Germany have developed a personalised immune therapy for skin cancer.

In the last ten years or so the rates malignant melanoma, which is a form of skin cancer, have doubled. But our ability to cure the disease has remained pretty dismal, with 5 year survival rates as low as 10% for patients who present with a cancer that is already spreading.

This week there's some good news though: two teams of researchers, one at Johannes Gutenberg University in Germany and the other at the Dana-Faber Cancer Institute in the US, have independently developed strategies, published this week in Nature, for producing personalised anticancer "vaccines".

The new vaccine approach triggers the production of immune T cells that can single out chemical differences between a patient's cancer cells and their healthy tissue to attack exclusively the cancer and leave healthy tissue unharmed.

It relies on the fact that cancers make a lot of genetic spelling mistakes - called mutations - when they copy their DNA. These DNA changes lead to subtle and cancer-specific changes to the protein markers that cells display on their exteriors.

By sensitising the immune system to these altered markers, the vaccines lead to the production of anti-tumour T cells called CD4 and CD8 lymphocytes, which wipe out the cancer cells but, crucially, do not touch healthy cells.

Both groups began by reading the DNA codes from tumours collected from human patients. These were compared with codes prepared from the patient's healthy tissue, so that the pattern of changes unique to the cancer could be identified. A computer algorithm was then used to pinpoint those changes most likely to result in differences to the cancer cells external markers.

A shortlist of some 10-20 were then selected for fashioning into vaccines. The US group developed their vaccine by synthesising the altered proteins corresponding to the mutated genes in the cancer, while the German team used what is called an RNA vaccine. This is where a short piece of genetic material called RNA, which can be read by cells and turned into proteins, is injected in place of the protein itself.

In both cases, human cancer patients who received the vaccines did not show side effects but did develop high levels of immune anti-cancer activity. Cathy Wu, who leads the US group, tested her vaccines on 6 melanoma victims.

"In the two year follow up period, none of the patients have had disease relapse. Patients like this would normally have a 50% chance of their disease returning." The German team saw similar success rates in the 13 patients they enrolled.

According to Wu, the technique owes its success to the fact that it offers personalised vaccination against an individual's own disease. Encouragingly, the generic approach they have taken also means that the technique can be translated to other cancers too.

"We're setting up other studies now into ovarian, bowel, some blood cancers," says Wu.

Overall, she's optimistic, but cautious. "This was a first foot-through-the-door Phase 1 trial. It's a small number of patients. Now we need to follow up with a larger patient group and a longer follow up."

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