In a new step in cancer immunotherapy, researchers have found that even if one’s own immune cells cannot recognise and fight their tumours, borrowing someone else’s immune cells might help. The study shows that adding mutated DNA from cancer cells into immune stimulating cells from healthy donors creates an immune response in the healthy immune cells.
Inserting the targeted components from the donor immune cells back into the immune cells of the cancer patients, Ton Schumacher of the Netherlands Cancer Institute and Johanna Olweus of the University of Oslo in Norway were able to make cancer patients’ own immune cells recognise cancer cells.
There are a number of possible causes that can prevent the immune system from controlling cancer cells. Helping the immune system to better recognise cancer cells is one of the main focuses in cancer immunotherapy.
Schumacher and Olweus decided to test whether a ‘borrowed immune system’ could “see” the cancer cells of the patient as aberrant.
The recognition of aberrant cells is carried out by immune cells called T cells. All T cells in our body scan the surface of other cells, including cancer cells, to check whether they display any protein fragments on their surface that should not be there.
Upon recognition of such foreign protein fragments, T cells kill the aberrant cells. As cancer cells harbour faulty proteins, they can also display foreign protein fragments - also known as neo-antigens - on their surface, much in the way virus-infected cells express fragments of viral proteins.
To address whether the T cells of a patient react to all the foreign protein fragments on cancer cells, the research teams first mapped all possible neo-antigens on the surface of melanoma cells from three different patients.
In all three patients, the cancer cells seemed to display a large number of different neo-antigens. But when the researchers tried to match these to the T cells derived from within the patient’s tumours, most of these aberrant protein fragments on the tumour cells went unnoticed.
They tested whether the same neo-antigens could be seen by T-cells derived from healthy volunteers. Strikingly, these donor-derived T cells could detect a significant number of neo-antigens that had not been seen by the patients’ T cells.
“In a way, our findings show that the immune response in cancer patients can be strengthened; there is more on the cancer cells that makes them foreign that we can exploit. One way we consider doing this is finding the right donor T cells to match these neo-antigens,” said Schumacher.
“The receptor that is used by these donor T-cells can then be used to genetically modify the patient’s own T cells so these will be able to detect the cancer cells,” he said. The study was published in the journal Science.