Why do some cancers no longer respond to therapy? And why do tumors succeed in evading the immune system? These questions were at the heart of a research project on resistance in B-cell lymphomas.
Why do some cancers no longer respond to therapy? And why do tumors succeed in evading the immune system? These questions were at the heart of a research project on resistance in B-cell lymphomas.
Despite major advances in cancer medicine, the treatment of recurrent or therapy-resistant tumors remains a major challenge, particularly when cancer cells are no longer recognised as such by the immune system.
The project supported by Swiss Cancer Research pursued a novel approach. Instead of targeting the tumor directly, the early-career researcher Dr Justine Epiney investigated how the metabolism of cancer and immune cells influences their interaction. Cellular metabolism, which describes how cells take up and process nutrients, plays a central role in determining how active immune cells are and how effectively they can combat tumor cells.
To identify new therapeutic entry points, several thousand molecules were systematically screened. The aim was to find substances capable of enhancing the immune response against the tumor. In this process, the researchers identified a particularly promising small molecule called PhagoBooster One (PB1).
PB1 was found to affect tumor cells and the immune system in different ways. The molecule blocks an enzyme involved in the production of certain fatty acids that are very important for the proper function of the cell membrane of cancer cells. By disrupting the production of these lipids, PB1 alters the tumor cells’ surface in a way that makes them easier for the immune system to recognise. Tumors that previously managed to evade immune surveillance thus become more vulnerable.
At the same time, PB1 interferes with the metabolism of immune cells by modifying how they generate energy. As a result, they increasingly rely on sugar rather than fats as an energy source, which improves their function. PB1, therefore, acts as a booster of the natural immune response, making our immune system more efficient at infiltrating and killing tumors.
In preclinical mouse models, PB1 was shown to slow tumor growth and improve survival without causing relevant side effects. These findings suggest that PB1 could in the future be developed as an add-on to existing treatments, particularly immunotherapies.
The results obtained form the basis for further studies. As a next step, the findings will be investigated in models that more closely reflect the clinical situation, for example using patient samples. In addition, a patent has been filed to support the further therapeutic development of PB1.
Epiney conducted the project as part of her doctoral training with the support of an MD-PhD fellowship from Swiss Cancer Research foundation. She has since begun her clinical training in haemato-oncology. The close connection between research and clinical practice is particularly important to her.
Project number: MD-PhD-5595-06-2022
The project is made possible by Swiss Cancer Research in collaboration with the BRYN TURNER-SAMUELS Foundation.
