What is immunotherapy?

Immunotherapy is a treatment that aims to "mobilize" the patient's immune defenses against his disease. This is an important way for current cancer research. Several immunotherapy treatments are already available. 

Our immune system

Our body is protected by an immune system. It is made up of specialized cells produced by the bone marrow, which are mainly present in the blood, the lymph nodes, the spleen, and the tissues. They protect the body against external attacks (microbes, viruses, etc.). These "invaders" are detected, identified, attacked, and eliminated by the immune system. They should also recognize and destroy cancer cells. Yet they are often unable to do so. Immunotherapy research provides a better understanding of how cancer cells escape immune defenses. The goal of immunotherapy treatments is to restore the immune system's ability to act on cancer cells.

Immunotherapy and cancer: where are we? 

Numerous clinical trials of immunotherapy are in progress, both in Belgium and abroad. Immunotherapy is gradually taking its place in the treatment of certain cancers, alongside surgery, radiotherapy, and chemotherapy.

 By eliminating the last cancer cells that have escaped other treatments, immunotherapy could, for example, transform a remission (disappearance of all signs of the disease, before a subsequent recurrence) into a permanent cure. 

Why doesn't the immune system eliminate cancer?

Scientists have tried to answer this question. They first thought that cancer was not recognized as such by the immune system. After all, a cancer cell comes from a normal, more or less "modified" cell. However, this modification of the cell's "identity card" may not be sufficient to trigger an immune reaction.

Research has shown that immune defense cells are able to respond to cancer cells. But it happens that this immune reaction is too weak or too late to be effective.

In fact, cancer cells do not wait passively for the immune system to activate. Certain cancer cells can develop a "camouflage" or even take the initiative and block the action of the immune defenses.

In short, our defenses are faced with an "invader" difficult to target.

Immunotherapy treatments

Bispecific antibodies: bringing immune cells closer to tumor cells

Bispecific antibodies work by activating the immune system to destroy cancer cells. They are called bispecific because they can bind to two different cells, cancer cells, and immune cells, for example, T lymphocytes. The antibody, by allowing the bringing together of these two types of cells, thus facilitates the elimination of cells cancerous by T lymphocytes. Blinatumomab is the first antibody in this class. It was authorized in November 2015 for the treatment of acute lymphoblastic leukemias.

Adoptive cell transfer: selecting or creating more powerful immune cells

Research is focusing on other approaches to immunotherapy; adoptive cell therapies also called adoptive cell transfer. These treatments aim to stimulate the patient's immune system by giving immune cells the information they need to better recognize tumor cells as abnormal and thus be able to attack them. For this, immune cells are selected and/or modified in the laboratory and then reinjected into the patient's body.

A first approach, the adoptive transfer of infiltrating T lymphocytes (TIL for tumor-infiltrating lymphocytes), consists of taking T lymphocytes from a patient from samples of his tumor, selecting the most effective, cultivating them in the laboratory in large number and then reinject them. The responses obtained with these therapies being very variable, new strategies had to be thought of.

 A more recent approach is not only to select immune cells but to modify them genetically. It is the adoptive transfer of genetically modified T lymphocytes, also called CAR-T. In this type of treatment, immune cells, T lymphocytes, are taken from the patient's blood and then genetically modified in the laboratory to express specific receptors on their surface. These receptors will allow the modified cells and then called CAR-T, to identify antigens present on the tumor cells. These cells, once modified, are cultivated in the laboratory until they proliferate by the millions and are then re-injected into the patient's body, where they continue to multiply. Due to their receptors, they will then be able to specifically recognize and destroy cancer cells.

This immunotherapy approach has already been used for a few years, in the context of clinical trials, for the treatment of acute lymphoblastic leukemia, particularly in the United States. Despite very encouraging results in the treatment of certain malignant hemopathies, many challenges remain today. The results of these treatments are indeed more modest for solid tumors in particular, and potentially very significant toxicities have been reported; several deaths occurred during trials on these treatments. Research is currently being carried out to better understand the immune response induced by these genetically modified T cells and thus allow safer administration of this type of therapy.

Some research now focuses on the transfer of cells from healthy donors and not from the patient himself. These "standardized" cells could then be produced in advance and would, therefore, be available at any time. A first clinical trial in children started in mid-2016 in London, is currently testing these treatments in acute B-cell lymphoblastic leukemia (B-ALL). However, it will take several years before such treatments are available on the market.

Therapeutic vaccination: pitting the immune system against a specific target

Therapeutic vaccines are not intended to prevent the onset of disease, like preventive vaccines, but are designed to treat, or help treat, cancer that is already present.

The goal of therapeutic vaccination is to stimulate and direct a patient's immune system specifically against cancer cells.

Different types of therapeutic vaccines are currently in development or undergoing clinical trials. These vaccines can be designed from cancer cells, cell fragments, antigens, or even immune cells. Some therapeutic vaccinations involve introducing antigens into the patient's body. The recognition of this antigen leads to an immune response, which will activate T lymphocytes or the production of antibodies to fight against the cells carrying these antigens. In recent years, research has gone further by seeking to develop personalized vaccines, tailor-made for each patient.

For this, a genetic analysis of the tumor is carried out. This analysis identifies the mutations responsible for the presence of certain proteins on tumor cells. These proteins, or neo-antigens, are specific to each tumor. This information helps to design a personalized vaccine that will target these proteins. Once injected into the patient's body, the vaccine allows the immune system to recognize tumor cells, carriers of these proteins, and stimulates the production of immune cells capable of destroying them.

Designing effective therapeutic vaccines is difficult, and research continues. Vaccines must indeed be able to stimulate an immune response against the right target and in a sufficiently effective way to overcome the means used by cancer cells to escape the immune system.

Author: Vicki Lezama