Researchers have developed a new way to identify the right molecules for personalized cancer immunotherapy.
The goal is a vaccine that would cause cancer-repelling T cells to multiply in the body, thereby strengthening the body’s immune defenses.
Since on the one hand tumors differ greatly from patient to patient, and on the other no two people (except identical twins) have the same immune system, future immunization against cancer is a complex example of personalized medicine. The goal is to develop an individual vaccine for each patient.
Like keys in locks
Potential vaccines include pieces of proteins, known as peptides, which are found only in tumors due to a mutation. Because T cells are specific and always recognize only one particular peptide, just as a key fits only one lock, a further prerequisite for a vaccine of this kind is that the patient has T cells capable of recognizing these cancer peptides in the first place.
So before doctors can immunize a cancer patient, laboratory tests must occur to search for corresponding pairs of T cells and peptides. A peptide that is recognized by a T cell can be used for personalized immunization. The vaccine should then activate the T cells in the body that recognize only that peptide (and thus tumor cells). These T cells should ultimately wipe out the tumor.
The new method makes it possible for a laboratory to determine which T cells recognize which peptide. Up to now this has been incredibly difficult. Scientists at ETH Zurich used tumors in mice to show that their approach works. Next, they want to demonstrate the effectiveness of their approach in dealing with tumors in humans.
Reporter cells
At the heart of this new method lies a collection of several million reporter cells, each one of which presents on its cell surface one of many peptides found in a tumor. The reporter cells are designed to turn green as soon as a T cell interacts with them, alerting scientists to those tumor peptides that a cancer patient’s T cells recognize.
This involves mixing the collection of reporter cells with T cells from the patient’s tumor, isolating the reporter cells that turn green, and identifying the peptide they carry.
The scientists must produce a different set of reporter cells for each patient. “One option is to determine the tumor’s genetic sequence and compare it with the gene sequence of the patient’s healthy cells,” says Manfred Kopf, professor of molecular biomedicine. This lets the researchers determine how much the tumor differs from healthy tissue and then transfer the genetic information with precisely these tumor-specific differences into the reporter cells.
Algorithms or this test?
As Kopf explains, “Other scientists are using computer predictions to try and find out which cancer peptides are suited to this type of immunization. But this approach is only as good as the algorithms used—and at the moment, they aren’t very reliable. By contrast, we have developed an experimental test that assures us that the T cells recognize patient tumor peptides.”
Initial tests involving a breast cancer model in mice showed Kopf and his colleagues that their method works. In immunized mice, the immune system did indeed attack the tumor; in the non-immunized mice that the scientists used as a control, this did not happen.
“Essentially, our technique and personalized immunization hold out promise for the treatment of all cancers—especially in combination with checkpoint inhibitors,” Kopf says, adding that the technology could also be useful for the research and treatment of autoimmune diseases such as multiple sclerosis or type 1 diabetes.
This research appears in Nature Immunology.
The scientists patented this method five years ago. To develop commercial applications for the technique, the scientists founded a spin-off company called Tepthera.
Source: ETH Zurich
