What is immunotherapy?
Immunotherapy against cancer comprises various procedures and active substances that help to direct the body’s own immune system against the cancer. Immuno-oncology thus represents a fourth pillar of cancer therapy – alongside surgery, radiotherapy and chemotherapy.
Not suitable for all patients
Immunotherapy for cancer is usually only used when conventional treatment has failed. How successful it is depends on many factors. One of these is the type of cancer. Two examples:
In metastatic non-small cell lung cancer, immunotherapy extends the life of patients by several months on average. In the case of advanced malignant melanoma, patients who would otherwise be very likely to die quickly may even gain several years.
Immunotherapy: cell biological background
Normally, diseased and outdated body cells die on their own. Doctors call this programmed cell death “apoptosis”. Cancer cells are different. They continue to divide and replace healthy tissue.
As part of immunotherapy, white blood cells (leukocytes) are stimulated to render the cancer cells harmless: T cells and natural killer cells – two representatives of the lymphocyte subgroup – are supposed to fight the cancer in the same way as invading pathogens.
Cancer cells trick the immune system
Although other cancer cells are recognized by the immune cells, they manipulate or weaken the immune system – for example, by presenting inhibitory signaling molecules on their surface to the T cells so that they no longer attack.
Immunotherapy – balance between activation and moderation
Cancer cells therefore use very different regulatory mechanisms to trick the immune system. Scientists summarize the various strategies under the term “immune escape mechanisms”. Accordingly, there are also different approaches in immunotherapy to make the cancer cells vulnerable after all:
Immunotherapy with cytokines
For example, the activity of the immune system can be boosted with the help of interleukin-2. Interferon, in turn, slows down the growth and division of cells – including cancer cells.
Disadvantage: Compared to newer methods of immunotherapy, cytokines do not have a targeted effect. They are only successful with a few types of tumor.
Immunotherapy with monoclonal antibodies
Antibodies are Y-shaped protein molecules that attach themselves precisely to the specific antigens of a cell. They mark diseased cells and pathogens (such as bacteria) for the immune cells so that they can eliminate them. Precisely fitting antibodies can also be produced artificially.
On the other hand, monoclonal antibodies are also used as immuno-oncological therapeutics: If they attach to a tumor cell, this is a signal for the immune system to attack it. Monoclonal antibodies can also be used to send targeted cytotoxins or radioactive substances to the cancer cells, causing them to die.
And there is another possible application: monoclonal antibodies act as immunotherapy by inhibiting certain signaling pathways that are important for tumor growth. There are also immunotherapeutic antibodies that prevent the formation of blood vessels that supply the tumor.
Disadvantage: Immunotherapy using monoclonal antibodies only works with tumors that have very specific surface characteristics that do not or hardly ever occur in healthy cells. Even if the tumor is poorly supplied with blood vessels or is very large, the treatment has a poor effect as not enough antibodies reach the target.
Immunotherapy with therapeutic cancer vaccines
Research is being conducted into tumor vaccines, for example, which are designed to make the immune system aware of specific tumor antigens. For example, tumour antigens can be produced in large numbers in the laboratory and then injected into patients as a “cancer vaccine” – in the hope that their immune system will then recognize and attack these antigens on the existing tumour cells.
Dendritic cell therapy involves extracting dendritic cells from the body and equipping them in the laboratory with antigens that are characteristic of specific cancer cells and do not otherwise occur in the body. These “armed” immune cells can then be administered to the patient in order to accelerate the immune system’s fight against the cancer – or so the idea goes.
In preparation for CAR T-cell therapy, patients receive light chemotherapy. This not only eliminates some of the cancer cells, but also the T cells. This increases the effectiveness of the subsequent CAR-T cell therapy.
Disadvantage: So far, success has been moderate. No tumor vaccines have yet been approved for cancer therapy; however, some candidates are at least being used in clinical trials. Dendritic cell therapy is also not yet standard in cancer treatment. The very complex and expensive CAR-T cell therapy is currently only possible for selected patients with certain forms of cancer.
Immunotherapy with immune checkpoint inhibitors
Some tumors can activate these immune checkpoints, i.e. trigger their braking function: They carry molecules on their surface that match certain T cell receptors, which function like turn-off buttons. Upon contact, the T cell is inactivated and does not act against the cancer cell.
Immune checkpoint inhibitors can be used to counteract this – they release the “brakes” again by occupying the critical surface molecules of the cancer cells. This means that they can no longer operate the T-cells’ switch-off buttons. As a result, the T cells can take action against them.
When is immunotherapy carried out?
There are currently only suitable immuno-oncology drugs for some forms of cancer. Some of these are only administered within the framework of studies. The active substances developed to date for cancer immunotherapy and their areas of application include
Monoclonal antibodies – this form of immunotherapy can be considered for the following forms of cancer, for example:
- breast cancer
- colorectal cancer
- Non-Hodgkin’s lymphoma (NHL)
- Non-small cell lung cancer (form of lung cancer)
- Kidney cancer
- Leukemia (“blood cancer”)
- Multiple myeloma (plasmacytoma)
Checkpoint inhibitors – they are available for the treatment of the following tumor forms, among others:
- Malignant melanoma (black skin cancer)
- Renal cell cancer (renal cell carcinoma)
Cytokines – areas of application include
- Skin cancer
- leukemia
- renal cell cancer
CAR-T cell therapy can be used in certain cases of non-Hodgkin’s lymphoma and leukemia.
What do you do with immunotherapy?
What are the risks of immunotherapy?
Fighting cancer in a gentle way has hardly been possible to date. Immunotherapy can therefore also have side effects. However, these are different from the side effects caused by chemotherapy. For example, patients do not usually lose their hair.
The use of cytokines such as interferon can cause flu-like symptoms such as fever, fatigue, loss of appetite and vomiting. Interferon also has an effect on the nervous system. In individual cases, it can cause depression and confusion via this pathway.
What should I be aware of after immunotherapy?
Even if immunotherapies are specifically directed against cancer cells, they can be associated with considerable side effects. For this reason, immunotherapy against cancer should always be carried out in specialized centers. If you experience any symptoms afterwards, always discuss them with your doctor. Especially if the immune system is activated too strongly, it is important to quickly restore the balance during immunotherapy.
