Background

One way of treating cancer is to use the patient’s own immune cells. Tumours contain T cells that have already found their way in and recognised the cancer, called tumour-infiltrating lymphocytes. In this treatment they are taken out, grown in large numbers, and given back. The difficulty is getting enough of them, and getting them active enough to work.

María Cruz Cobo’s group at the University of Geneva has identified compounds intended to improve both. Testing them is the problem. Mice are the standard route and they fit this question badly. Mouse T cells are difficult to grow out of tumours in useful numbers, and human T cells put into mice with weakened immune systems tend to attack the animal itself, which obscures whatever the experiment was meant to show.

There is an alternative that uses human tissue throughout. A fragment of a patient’s tumour is embedded in a collagen matrix and kept alive for a short period. Because it is a piece of the actual tumour, it arrives with its own immune cells and supporting tissue intact, which most organoid systems lack. That makes it possible to watch T cells move into the tumour and kill its cells, and to test whether a compound improves that.

Mitchell Levesque’s group at the University of Zurich adapted this approach for melanoma and published it in 2023. The method is demanding in practice, particularly the handling of fresh tumour tissue, and learning it reliably requires working alongside people who already do it. This grant funded two periods there.

Aims

• Learn to prepare three-dimensional cultures from fresh patient melanoma tissue, including the tissue handling and digestion steps that determine whether the culture survives.
• Learn to assess T cell behaviour within the cultures: whether they become activated, move into the tumour tissue, and kill tumour cells.
• Establish the method at the University of Geneva and apply it to testing the group’s own compounds.
• Train others in it, within the group and in two collaborating labs.
• Share it more widely, through a workshop with the university’s organoid facility and a presentation at the Basel Cell Therapy Symposium.