A new step in cancer immunotherapy: researchers from the Netherlands
Cancer Institute and University of Oslo/Oslo University Hospital show that even if one's own
immune cells cannot recognize and fight their tumors, someone else's immune cells might.
Their proof of principle study is published in the journal Science on May 19th.
The study shows that adding mutated DNA from cancer cells into immune stimulating cells
from healthy donors create 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, the researchers were able to make cancer patients' own immune cells recognize
The extremely rapidly developing field of cancer immunotherapy aims to create
technologies that help the body's own immune system to fight cancer. There are a number
of possible causes that can prevent the immune system from controlling cancer cells.
First, the activity of immune cells is controlled by many 'brakes' that can interfere
with their function, and therapies that inactivate these brakes are now being tested in
many human cancers. As a second reason, in some patients the immune system may not
recognize the cancer cells as aberrant in the first place. As such, helping the immune
system to better recognize cancer cells is one of the main focuses in cancer
Ton Schumacher of the Netherlands Cancer Institute and Johanna Olweus of the University
of Oslo and Oslo University Hospital 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 harbor
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 3 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 tumors, most of
these aberrant protein fragments on the tumor cells went unnoticed.
Next, 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.," says Ton 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."
"Our study shows that the principle of outsourcing cancer immunity to a donor is sound.
However, more work needs to be done before patients can benefit from this discovery.
Thus, we need to find ways to enhance the throughput. We are currently exploring
high-throughput methods to identify the neo-antigens that the T cells can "see" on the
cancer and isolate the responding cells. But the results showing that we can obtain
cancer-specific immunity from the blood of healthy individuals are already very
promising," says Johanna Olweus.
This research was performed within the K.G.Jebsen Center for Cancer Immunotherapy, at the
University of Oslo/ Oslo University Hospital and The Netherlands Cancer Institute.