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 was 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 cancer cells.
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 immunotherapy.
Borrowed immune system
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.
Finding a match
"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
"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.