Predicting the effects

Dermatologist Florentia Dimitriou, and Ken Kudura of the USZ Department of Nuclear Medicine, plan to personalize immunotherapy for skin cancer. The idea is to make sure every patient gets the right therapy, with as few side-effects as possible.

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It looked like a birthmark, that’s all! Annabelle Gschwind* had noticed that the dark patch on her shoulder had gotten bigger. But skin cancer at the age of 54? She couldn’t get to grips with the diagnosis: the melanoma had already metastasized in her liver.

Melanoma is becoming increasingly frequent in western countries, especially in Switzerland. If discovered early on the prognosis is good. But if metastases have already formed, so far patient life expectancy has been low. For a number of years already immunotherapy has been a source of hope. It’s now also being used to treat Annabelle Gschwind. It involves using artificial antibodies to activate the immune cells of the natural defense system. Unfortunately they then attack not only cancer cells, but the healthy cells of the body as well. There are almost always side-effects such as skin rashes or inflammation of the thyroid, liver or intestine, triggered among other things by specific proteins called cytokines in the blood.

Florentia Dimitriou, a resident at the Department of Dermatology at University Hospital Zurich (USZ), aims to avoid these side-effects. She’s analyzing the blood of around 200 patients receiving immunotherapy. Her hypothesis is that each person has their own individual pattern in terms of what cytokines are activated in the blood. From this individual “cytokine profile” it’s also possible to tell what side-effects that particular person might suffer. If this theory is confirmed, it will be possible to treat the side-effects of an immunotherapy in a much more targeted manner than was previously the case. At present, patients with side-effects are given cortisone for the inflammation. Thanks to the “cytokine profile” it will be possible to use agents very specifically to block only the activated cytokines. “That would enable much more personalized treatment,” says Florentia Dimitriou.

New biomarkers

Monitoring immunotherapy is also a challenge. Basically a reliable way of tracking the course of cancer is to use PET/CT imaging. Marked sugar molecules injected into the patient make cancer cells visible. This is because these cells consume a lot of energy.

With immunotherapy it’s more difficult: processes set in motion by the activated immune cells also use a lot of sugar. “So it’s not always clear whether the images show a continuation of the cancer or a desired immune reaction,” explains Ken Kudura, a resident at the USZ Department of Nuclear Medicine. He’s trying to recognize patterns allowing a clear interpretation of the PET/CT images of patients with metastasized melanoma. He wants to define immunological responses as biomarkers that indicate whether the immunotherapy is working. “If a patient’s not responding we can quickly switch to another therapy,” explains Kudura.

The two researchers’ projects are supported by a donation from the Iten Kohaut Foundation to the USZ Foundation – to enable patients such as Annabelle Gschwind to get even greater benefit from immunotherapy, ideally without side-effects.

*anonymized/symbolic image

100% financed

Iten Kohaut Foundation