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Cells fit for the fight against cancer CAR T-cell therapy can be a powerful means of treating cancer, where a patients’ own T cells are extracted and modified, before being then re-introduced back into the patient to attack the cancer. Researchers in the CellFit project are working to develop new, more effective methods of producing T cells and assessing their efficacy, as Dr Else Marit Inderberg Ph.D explains. The emergence of Chimeric Antigen Receptor T-cell (CAR T-cell) therapy gives clinicians a powerful option to treat certain types of cancer. In CAR T-cell therapy, a patients’ own T cells are extracted and modified to enhance their effectiveness as part of the immune response, then more of these cells are grown in the laboratory before being re-introduced back into the patient to attack the cancer. “CAR T-cell therapy is approved for certain haematological malignancies, and clinical trials are ongoing for some solid cancers as well,” outlines Dr Else Marit Inderberg, Head of the Translational Research Unit at Oslo University Hospital. The tumour microenvironment around a solid cancer forms a kind of protective layer however, limiting the effectiveness of CAR T-cell therapy against solid cancers. “There may be physical barriers like proteins that make it hard for T cells to penetrate a tumour. Or some cells may produce immuno-suppressive agents that will prevent the immune cells from doing their job,” says Dr Inderberg.
CellFit project As the Principal Investigator of the CellFit project, Dr Inderberg is part of a team developing new methods of producing engineered T cells and evaluating their efficacy. The project brings together partners from both the academic and commercial sectors, with the ultimate aim of improving cancer treatment. “We’re trying to develop
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“Overview of CellFit activities”. Credit: Léa Rosselle
new methods so that we won’t need as many T cells in future when treating patients. The hope is that these T cells will stay in the body for much longer, and they will be able to then function more effectively,” she explains. The T cells initially taken from patients’ blood are typically quite heterogenous; one important sub-type are the memory T cells, which can persist in the body and attack a cancer should it recur. “When we vaccinate people, or we see that they’ve had an infection previously, they have a pool of memory T cells that are ready to attack the infection if it comes back,” says Dr Inderberg. “We think that these more stem-cell like memory T cells would be able to persist in the body for much longer.”
The cells infused in CAR T-cell therapy are typically ready to attack cancer cells straight away, with receptors which enable them to identify and attack a tumour, yet there are also other factors to consider in terms of therapeutic effectiveness. The surrounding microenvironment is quite harsh for T cells, and they are in competition with tumour cells for nutrients, so Dr Inderberg says that cells with a less active metabolism are likely to be more effective in the long term. “We expect that we’re looking for cells which use less sugar, less glycolysis. If they need less nutrients they might be more likely to survive in the tumour microenvironment and function effectively,” she outlines. Once the cells have been
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