Identifying telltale markers for personalised lung cancer treatment

T cells play a crucial role in our immune system, helping us to fight infections and diseases by attacking pathogens such as viruses and bacteria. When primed to recognise specific antigens on the surface of cancer cells, they can also be used in cancer treatments.

As part of the EU-funded CANVAS project, researchers at the University of Gdańsk's International Centre for Cancer Vaccine Science (ICCVS) in Poland laid the foundations for a new T cell-based cellular therapy for non-small cell lung cancer (NSCLC).

The project brought together researchers from the University of Rome Tor Vergata in Italy, the French Alternative Energies and Atomic Energy Commission (CEA) and Polish biotech start-up Real Research, to develop the treatment further.

"Many previous studies on anticancer therapies have proven successful yet translations into cures for patients have failed," says Natalia Marek-Trzonkowska, director of ICCVS. "That's why we designed CANVAS: we wanted to understand how it happens, how the environment of the cancer model influences the tumour and its interaction with the immune system."

The project was enacted as part of Horizon Europe's Widening Actions, funding that helps to reduce disparities in research and investment funding and ultimately drive progress in cancer vaccine science across Europe.

Cellular therapy pilot

The central CANVAS pilot study focused on proteins found on the surface of most cells in the body. These proteins display chains of amino acids known as peptides, which T cells use to recognise foreign cells and trigger an immune response.

Researchers at ICCVS developed a method to separate and characterise these peptides, to see if any could be used to help T cells identify cancer cells. "We were curious if the repertoire of peptides presented by these molecules in cancer changes depending on the environment where the cancer is growing," explains Marek-Trzonkowska. The team assessed peptides in a patient, then in an in vitro culture in both 2D and 3D conditions, and finally in an animal model.

Through these collaborative efforts, researchers at ICCVS gained new experience from the project partners to help achieve their goals. Real Research provided knowledge of 3D cell culture, the University of Rome Tor Vergata offered expertise in patient-derived xenograft animal models, and CEA in France delivered skills in big data analysis.

"CANVAS workshops and training visits increased our capacity to conduct ambitious projects and enabled realisation of the pilot study, which delivered important information," notes Marek-Trzonkowska.

How environment affects cancer recognition

The project showed for the first time how much the environment alters cancer features recognised by the immune system. This is crucial information for ensuring T cell therapies can recognise cancer targets.

The team found that peptide repertoires differ significantly in cancer models from the primary tumour, which means immune cells that can kill cancer in vitro may not recognise the same cancer in human or in animal models. "While this isn't the most positive discovery, there are bright aspects too and both can be used in development of future anticancer therapies," says Marek-Trzonkowska.

The researchers also discovered unique features of NSCLC shared by tumours from various patients, which are also preserved in in vitro and in vivo models of the cancer. "These cancer features are the proper targets for the anticancer therapy," adds Marek-Trzonkowska.

Finding targets for cancer immunotherapy

The researchers are proud they could prove something that others sensed but nobody could demonstrate, while also finding several unique features which could become targets for precise and safe immunotherapy for cancer.

"Now we understand better how to use experimental models to treat cancer in humans," remarks Marek-Trzonkowska. "The gained knowledge is a foundation on which we will build the therapy."