Text: Catherine Cossy

"I had to wait five days – it was a long time"

Patients

Once consent has been given, taking a surgical sample is the next moment of truth: patients can only proceed with the trial if the lymphocytes taken from the tumour multiply correctly in the laboratory.

It all started out with a simple birth mark on his buttock, which Angelo* had forgotten all about. But in 2006 it started to spread, doubling in size. The diagnosis was clear: melanoma. For Angelo, it was a complete surprise. "Before, I used to play a lot of sport, especially football. And I worked on building sites. I was never ill. No doctor had ever said I should keep on eye on my birth mark. I wish it had been checked regularly for any changes," he now confides.

Following chemotherapy and an additional immunotherapy treatment, he finished his first round of treatments in the summer of 2009. But in 2014, Angelo’s cancer returned, with metastases in his lungs and liver. He was again treated with immunotherapy until the summer of 2018, with limited success. It was then that his doctor suggested he take part in the clinical trial called "ATATIL", whose principal investigator is Prof. George Coukos, head of the Immuno-Oncology Department at UNIL-CHUV and immuno-oncology services. Angelo, who is 44, lives near Coire, in Les Grisons, and travels across Switzerland for his treatment at CHUV, in Lausanne. He agrees to sign the consent form and then has to be taken to the operating theatre for stage 2 of the protocol: the removal of surgical samples.

A decisive intervention

"The first thing we do is schedule a biopsy," explains Virginie Zimmer, clinical research assistant in the Oncology Department at UNIL-CHUV. "Once we’ve taken the sample, we can determine whether there are sufficient numbers of tumour-infiltrating lymphocytes (or TILs) to ensure that the first phase of culturing cells in the laboratory will be satisfactory. If there are, we will then schedule the surgery to do the resection."

Angelo remembers the operation, followed by a period in hospital, as a difficult time:

"I knew what was going to happen: they take a sample from a metastasis in the lung, isolate the lymphocytes and see whether they multiply. In my case, it took five days before the numbers started to increase. It was a long time."

Even when they seem to be running down the clock, it is these cells that are decisive. If the T lymphocytes fail to multiply as they should, or if something unexpected brings the sequence grinding to a halt, the patient may not be able to have the treatment. "Unfortunately, a technical problem can occur, even though we do everything to ensure it happens as infrequently as possible," explains Virginie Zimmer. "It’s also why we’re running this trial: to check the feasibility of a treatment of this kind. It could also be the case that everything goes smoothly from a technical point of view, but the cells don’t multiply quickly enough to be re-infused." However, if a patient has to be removed from the protocol, they may be invited to take part in other clinical trials or follow a standard treatment regime.

Given the risk, did Angelo have any hesitation about taking part? "I didn’t have any other options, apart from removing my liver and I'm not afraid," he concludes gravely, noting that this experimental treatment has already been tested in the United States.

*Real name known to editor.



Biopsy

The removal of a fragment of tissue or organ for microscopic examination.

Resection

The full or partial removal of a diseased organ or tissue, retaining or re-establishing the function of the system of which it forms part.

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