Our immune system
The human immune system protects the body from damage caused by infectious diseases by recognizing “intruders” as foreign and fighting them off, while at the same time preserving healthy tissue or allowing it to regenerate. First of all, cancer is the body’s own tissue, i.e. it is not fundamentally foreign. However, this carries genetic changes that trigger the uncontrolled growth and do not occur in this way in healthy tissue. However, these changes are often “hidden”, do not show up sufficiently on the tumor cell surface, and increase only slowly in type and quantity. This then leads to the fact that the tumors are very similar to healthy tissue and that the patient’s own immune system either cannot recognize the changes at all and is not activated. Or the change is detected but the immune response is suppressed, meaning that a kind of tumor immune tolerance occurs. The result is an absent or insufficient immune response and thus a growing tumor.
What is immunotherapy?
Tumor immunotherapy” is an umbrella term for very different approaches that use the body’s own immune system as an ally in the fight against cancer.
Targeted immunotherapies are directed against specific molecules on the surface of cancer cells and thus have a more specific effect than classical chemotherapies. These therapies represent important steps in the direction of harming only the tumor, if possible, and sparing the healthy, vital tissue.
What are the types of immunotherapy?
Immunotherapies can either be immunotherapeutic agents administered from outside, e.g. as an infusion (e.g. antibodies against tumor cells that are not normally produced by the body in this way) or, in the case of a shutdown of the patient’s own immune system, the immune system can be activated by releasing the “brakes” of the immune system, so to speak, and thus lifting the immune tolerance.
Checkpoint Inhibitors
In the type of immunotherapy that aims to release the brakes on the patient’s own immune system, we aim to strengthen the existing but inactive immune response so that it fights the cancer. The immune response is based on the fact that cancer cells may have a tumor antigen on their surface, i.e., they carry a surface feature that is different from healthy tissue. This allows the tumor cell to be perceived by the immune system as a type of foreign cell. Some tumors have many of these different surface features, while others have few of them. In addition, tumors can also produce specific “brake molecules” for the immune system. It is interesting and logical that immune activation therapy of the patient’s own immune system usually works well precisely in those patients whose tumors carry many different surface features and many of these braking molecules compared to healthy tissue. By overriding the braking or control signal – the substances are also called “checkpoint inhibitors” – an immune response against the tumor then occurs.
A side effect of this activating immunotherapy can be that the brakes of other immune cells are also released and thus side effects occur that correspond to autoimmune diseases, i.e. that the immune system attacks healthy tissue as well. So there is a problem of selectivity here. However, depending on the type of cancer, the resulting side effects can be accepted and in some cases well controlled. Overall, one can assume fewer and different side effects than with classical chemotherapy.
Antibody
In addition to the above-mentioned activation of the patient’s own immune system, there are immunotherapies in which structures of the immune system are produced externally. These are then infused. The simplest and classic example is so-called antibodies, which go to tumor cell surfaces and attack them. Either the targets of the antibodies are tumor-specific (this is rare) or the targets are also present on healthy tissues but in lower density, or the tissue can be temporarily dispensed with and it regenerates after therapy.
Artificial antibody constructs
Recent developments in so-called “designer immunology” show that it is also possible to produce antibodies or antibody fragments to which one can then couple either chemotherapy or radiotherapy or cell messengers and deliver them relatively selectively to the tumor. Similarly, antibodies can be produced that act as an activating bridge between the tumor cell and the body’s own immune cell. That is, these antibodies stimulate the immune cell to kill the tumor cell.
CAR T cells
Another development is the genetic manipulation of the body’s own immune cells. In this way, antibodies can be introduced into “killer cells” so that they then attack the tumor cells with high selectivity. These include, for example, the so-called Chimeric Antigen Receptor (CAR) T cells.
For CAR T-cell therapy, white blood cells – so-called T lymphocytes – are taken from patients’ blood. These are then genetically modified in the laboratory so that they can recognize cancer cells. The optimized T lymphocytes are then administered back to patients via an infusion to target and destroy cancer cells. This type of therapy is only offered at a few, highly specialized centers in Switzerland.
More information
Manuel Schibli also benefited from the new possibilities of targeted immunotherapy. The 25-year-old from the canton of Aargau was diagnosed with acute lymphoblastic leukemia (ALL), a relatively rare cancer in adults. This specific form of blood cancer can be treated with CAR-T cells since a few years.
Research
In the field of immunotherapy, interdisciplinary teams of doctors and scientists work closely together at the CCCZ to develop new treatment approaches. The combination of innovative research and clinical expertise results in therapies that have the potential to sustainably improve cancer medicine. One focus is on the IMMUNO-CAR ZURICH program. The aim is to establish modern platforms for the efficient, safe and flexible production of CAR immune cells at the CCCZ. The Miracle study investigated the evaluation of the safety and immunological effects of CAR immune cells in glioblastoma. Another project, MACROCURE, is investigating the activation of macrophages against tumor cells.
Learn more about research at the CCCZ: Precision oncology projects – Comprehensive Cancer Center Zurich