Immunotherapy

The basic function of the immune system is to find and destroy abnormal cells, including tumor cells, and thus prevent the occurrence of cancer. It has been proven that in some people with cancer, so-called tumor-infiltrating lymphocytes (TIL) accumulate around tumor tissue, which is a sign of an immune response to the tumor, and such patients have a better prognosis than others. Despite the above, tumor cells have their own mechanisms by which they avoid the action of the immune system on them (genetic changes that make them less visible to immune system cells, proteins on the surface that suppress ("turn off") the immune response, the effect on normal cells around tumors that can interfere with the action of the immune system, etc.). Immunotherapy is a form of treatment that has been present in oncology for a long time, but only in recent years, after new knowledge about the functioning of the immune system, has it entered the treatment of cancer patients in a big way. It is a completely new concept of treatment, which treats cancer indirectly, unlike other forms of treatment. Namely, the goal of immunotherapy is not to attack cancer cells directly, but to enable the immune system to function adequately. Immunotherapy is most often administered intravenously, but some drugs are also administered orally (tablets or capsules), topically (application of cream to the skin for early skin tumors) or intravesically (directly into the bladder). There are several mechanisms on which immunotherapy can act, and therefore we have several groups of drugs:

​1. Immune checkpoint inhibitors are the most commonly used type of immunotherapy today (Figure 1). Checkpoints in a healthy person serve to prevent an overly strong immune response (which leads to autoimmune diseases), but tumor cells can use them to completely suppress its action. This occurs when T lymphocytes recognize and bind to a tumor cell. The checkpoint protein binds to a specific molecule on the tumor cell, and the tumor thus prevents the T lymphocytes from destroying the tumor cell. By blocking the aforementioned points with immunotherapy, such action by the tumor is prevented (the checkpoint protein is already occupied), so the immune system remains adequately activated. There are two basic types of drugs with this mechanism; They act on either CTLA-4 or PD-1/PD-L1 checkpoint proteins), and are currently used in the treatment of breast, bladder, cervical, colon, liver, lung, skin, stomach, head and neck tumors, and Hodgkin lymphoma.

Figure 1. The 2018 Nobel Prize in Physiology or Medicine was awarded to James Allison (USA) and Tasuku Honjo (Japan) for their discoveries in the field of immunotherapy. They made a particular contribution to the understanding of immune checkpoints.

2. T-cell transfer therapy (so-called adoptive immunotherapy) is a therapy that involves taking T-cells (a type of lymphocyte that is an important part of the immune system) from tumor tissue (Figure 2). It is assumed that those cells that are near the tumor are the ones that managed to recognize it as foreign tissue, but that there are not enough of them to adequately destroy it or to overcome the blocking signals from the tumor. The use of large numbers of such cells can bypass such barriers. The T-cells thus isolated are then further checked in the laboratory to select the most active clones, which are then multiplied in large numbers and returned to the patient through the blood. This method of treatment has so far proven to be the most effective for patients with melanoma, but numerous studies are ongoing.

3. Monoclonal antibodies are proteins produced in the laboratory that are designed to bind specifically to a certain target molecule according to the key-lock principle (targeted therapy) and are widely used in oncology today. Monoclonal antibodies are normally produced naturally in the body and enable the recognition of foreign bodies such as bacteria and viruses, and their role is similar when used as immunotherapy, where they facilitate the recognition of tumor cells. Another mode of action is to attract T lymphocytes to tumor cells so that they can destroy them.

​4. Therapeutic vaccines enhance the body's natural immune response to cancer cells. They differ significantly from conventional vaccines used to prevent infectious diseases, because they are administered to people who already have the disease (cancer). It is believed that cancer cells possess specific substances (antigens) that distinguish them from normal cells, and the use of vaccines stimulates the recognition and reaction to these antigens. Vaccines can be made from one's own tumor cells, from tumor antigens that most people with a certain type of cancer have, or from one's own dendritic cells (a type of immune cell that is important in recognizing foreign antigens in the body). One type of dendritic cell vaccine is currently the most widely used anti-tumor vaccine, and it is used in advanced stages of prostate cancer. In addition to anti-tumor vaccines in the narrow sense, this type of treatment sometimes includes oncolytic virus therapy, which uses viruses that can destroy tumor cells but not healthy ones (healthy cells successfully remove the virus).

Figure 2. Presentation of the phases of adoptive therapy with T lymphocytes. T lymphocytes are collected from the patient, the most active cells are selected which multiply and are then returned to the patient.

5. Immunomodulators affect specific parts or the immune system in general to enhance the immune response. The main types of this therapy are cytokines (proteins that are normally produced by white blood cells; examples are interferons and interleukins), BCG (a weakened form of the tuberculosis bacterium, which is routinely used in bladder cancer where it causes an increased immune response to the tumor) and various immunomodulatory drugs (thalidomide, lenalidomide, imiquimod and pomalidomide, which lead to an increased release of interleukin 2.

​Overall, the use of immunotherapy has achieved an extremely significant advance in the treatment of many malignant diseases, including melanoma, lung cancer, bladder cancer, head and neck tumors and others. What is particularly significant is that with the use of immunotherapy, for the first time in some patients, complete cure results have been achieved in patients with metastatic disease, which was not possible before. It should be noted that, since immunotherapy does not directly attack the tumor, some patients may need some time (sometimes several months) to show the effect of the treatment. In fact, in some patients, tumor lesions may even increase, and supervision by an experienced physician is required to distinguish disease progression from so-called pseudoprogression.

​What are the possible side effects? Although immunotherapy is generally tolerated extremely well and often without any significant changes for the patient, every drug can have side effects, including immunotherapy. They are mainly the result of excessive activation of the immune system, which then, in addition to Cancer cells can also attack healthy cells. Since the immune system works in a general way, any side effects can affect any organ or tissue of the patient (from the intestines, liver and lungs to the thyroid and all the others). Some side effects are known to occur early after the start of treatment, while others may occur with a delay. Skin reactions (pain, swelling, dryness, rash, redness, itching) and flu-like symptoms (fever, chills, weakness, fatigue, muscle and joint pain) can occur regardless of the type of immunotherapy, and rarely, allergic reactions to the drug can occur.

Continue reading:

Radiotherapy

Need more information about this topic? Contact us.