Personalized Cancer Vaccines Show Promise In Early Clinical Trials

The best defense against cancer may be our own immune system. PIcture above: Artist's impression of T-cells attacking a tumor in the body.

Jack Dunhill 14 Jul 2017, 17:42

Two first-stage clinical trials have successfully demonstrated the use of personalized vaccines against melanoma in humans. 

The aim of these two studies, published separately in the journal Nature, were not only to show a vaccine that is effective, but to show it is safe and should be tested in greater detail with a larger sample size. In the first study, six melanoma patients were tested and, after 25 months, four of them had no recurrence of the disease.

The other two were subject to repeat cases of the disease, as the cancer had already spread to their lungs by the time the study began. They subsequently received another treatment called anti-PD-1 therapy, and as a result the tumors completely regressed. This regression also came with an increased neoantigen-specific T-cell count, suggesting the vaccine was successful.

Following on from this, Ugur Sahin and his team tailored vaccines to 13 melanoma patients. Of these, eight patients were entirely cancer-free by 23 months. The T-cells had effectively infiltrated and destroyed the tumors, as a result of the vaccine creating a bolstered immune response specific to their cancer.

One of the difficulties in creating a vaccine against cancer is due to a mechanism in the body called "central tolerance", which prevents T-cells from targeting its own body cells. In this case, that also means it prevents T-cells from targeting tumors, as tumors are our own cells, after all. This is a difficult barrier to overcome when attempting to create a vaccine, as you effectively have to "teach" the immune system to target cancerous cells but not healthy ones. 

However, when a tumor-causing mutation arises in a body cell, markers (called "neoantigens") develop on the surface, which do not appear on healthy cells. By creating cancer vaccines with neoantigens specific to the patient, researchers may be able to overcome this barrier. With the recent introduction of massive parallel sequencing (MPS) technology, they can also evaluate mass amounts of neoantigens at a time and use this to generate predictions on which neoantigens will bind with which immune cells. 

Metastatic melanoma cells. NIH Image Gallery/Flickr
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