Immunotherapy Against cancer
Immunotherapy involves using the body’s immune defenses to attack and destroy cancer cells. Different approaches have been used for decades, before moving recently towards a very promising new strategy: targeting immune cells with drugs to break their tolerance towards cancer cells and thus stimulate their destruction by the body.
Our immune system has the ability to find and destroy cancer cells. But cancer cells sometimes hide from our immune system in order to avoid being destroyed. Cancer cells can also prevent the immune system from working properly. Immunotherapy helps strengthen or restore the ability of the immune system to fight cancer.
Immunotherapy is sometimes called biological therapy. You might also hear the word immuno-oncology, which is the study of how the immune system interacts with cancer cells to find out how to prevent or treat cancer.
The immune system and how immunotherapy works
The immune system defends and protects our body against infections and diseases. It is made up of organs, particular cells and substances that work together to find and fight germs, such as viruses or bacteria, or abnormal or unhealthy cells that cause diseases such as cancer. Germs and cancer cells have molecules called antigens on their surface that trick the immune system to find and destroy them. But some cancer cells manage to hide themselves from the immune system because they look a lot like normal cells. In some cases, the immune system is able to find cancer cells but is not strong enough to destroy all of them. Some cancer cells can even change the way the immune system responds, causing it to not work properly.
Immunotherapy strengthens the immune system or helps find and attack cancer. Immunotherapy is used to:
stop or slow the growth of cancer;
prevent cancer from spreading to other parts of the body;
help the immune system to be more efficient at destroying cancer cells;
delivering toxins, such as radiation therapy or chemotherapy, directly to cancer cells.
We are talking about a revolution in immunotherapy in the treatment of cancer, do you know why?
Immunotherapy differs from other cancer treatments in that it does not directly target cancer cells but the patient’s immune system. The treatments currently used aim to release or restore the action developed by the patient’s immune system against his tumor, in order to reduce it, or even eliminate it because of the “memory” specific to the immune system capable of recognizing and of eliminate a possible resurgence of cancer cells. We are currently experiencing the start of a real therapeutic revolution which should ultimately affect many types of cancer, thanks to the development of numerous drugs aimed at using the patient’s own immune defenses to fight against the tumor.
Is immunotherapy chemo?
Unlike chemotherapy, which seeks to destroy the tumor, immunotherapy helps the immune system recognize and get rid of cancer cells.
Types of immunotherapy
Different types of immunotherapy are used to treat cancer.
Monoclonal antibodies are designed in the laboratory. Just like the antibodies your immune system makes, their job is to trigger a reaction from the immune system. Some monoclonal antibodies find a specific antigen, such as a protein, in a cancer cell and bind to it. The immune system then knows it must attack and destroy these cells. An example of this type of monoclonal antibody is rituximab (Rituxan). Rituximab is used to treat certain types of non-Hodgkin lymphoma as well as chronic lymphocytic leukemia (CLL).
Monoclonal antibodies are also a targeted therapy because they block or target an abnormal gene or protein inside a cancer cell. They have other functions:
block growth signals and receptors that make cancer grow
giving radiation therapy or chemotherapy to cancer cells
Immune checkpoint inhibitors
The immune system normally prevents T cells, a type of immune cell, from attacking normal cells by using proteins called checkpoints. Checkpoints are part of a signaling pathway that the immune system uses to slow, or stop, an immune response. Some cancer cells can send signals that confuse T cells by activating a checkpoint signaling pathway and preventing them from attacking cancer cells. This allows the cancer to continue to grow since the cancer cells hide from the immune system.
Immune checkpoint inhibitors are monoclonal antibodies that block specific checkpoint proteins, allowing immune cells to attack and destroy cancer cells. It is used to treat melanoma, non-small cell lung cancer, kidney cancer and Hodgkin lymphoma.
Two immune checkpoint signaling pathways can be blocked to allow the immune system to fight cancer. PD-1 is an immune checkpoint that prevents T cells from attacking other cells. It does this by binding to PD-L1, a protein found on the surface of some normal or cancerous cells. There are cancer cells that contain a lot of PD-L1, which helps protect them from attack by T cells. Monoclonal antibodies, such as atezolizumab (Tecentriq), pembrolizumab (Keytruda), and nivolumab (Opdivo) ), target PD-1 or PD-L1 to help strengthen the immune system’s response to attack and destroy cancer cells.
CTLA-4 is another immune checkpoint on the surface of T cells that the monoclonal antibody called ipilimumab (Yervoy) can target, which helps boost the immune response against cancer cells.
Conjugated monoclonal antibodies
Monoclonal antibodies can be used to give radiation therapy or chemotherapy. Monoclonal antibodies used to deliver radiation therapy are bound to radioactive substances called radioisotopes. Antibodies find and attach to cancer cells before releasing radiation to destroy cancer cells.
When monoclonal antibodies are used to transport radioactive substances, this treatment is also called radioimmunotherapy. Ibritumomab (Zevalin) is a type of radioimmunotherapy. It is composed of a monoclonal antibody and the radioisotope yttrium-90. It is used to treat certain types of non-Hodgkin lymphoma.
Monoclonal antibodies are sometimes linked to chemotherapeutic agents to make antibody-drug conjugates. Brentuximab vedotin (Adcetris) is an antibody-drug conjugate that targets a protein on the surface of cancer cells in people with Hodgkin lymphoma. Trastuzumab emtansine (Kadcyla or T-DM1) is another type of antibody drug conjugate sometimes used to treat women with HER2 positive metastatic breast cancer.
Nonspecific immunotherapy uses cytokines, growth factors and other substances to strengthen the immune system so that it can fight cancer. Cytokines are chemicals in the body that cause the immune system to fight off diseases or germs that have entered the body. Cytokines can also be made in the lab and used to treat cancer.
Interferon is a type of cytokine secreted by the body. Interferon made in the laboratory to treat cancer is called interferon alfa (Intron A, Wellferon). Interferon can help trigger a stronger immune response against cancer cells and can also slow cancer growth or cause cancer cell death. Interferon alfa is used to treat melanoma and some types of blood cancer such as non-Hodgkin lymphoma and chronic myelogenous leukemia (CML).
Interleukin is another type of cytokine made by the body. Interleukin-2 (Proleukin) can be made in the laboratory. It helps the body to make more of certain types of immune cells that enhance the response of the immune system. It also helps the body make more antibodies against cancer cells, which allows the immune system to find and destroy cancer cells. Interleukin-2 is sometimes used to treat kidney cancer and melanoma.
Granulocyte colony stimulating factors (G-CSF) and granulocyte and macrophage colony stimulating factors (GM-CSF) are growth factors of blood cells that cause the bone marrow to produce more granulocytes and macrophages, two types of white blood cells that help fight infections. G-CSFs and GM-CSFs can also be given, together with other types of immunotherapy, to strengthen the immune system.
Bacillus Calmette-Guérin (BCG) is a type of bacteria that has been modified in the laboratory so as not to cause disease. It causes inflammation of the bladder, which triggers an immune response that helps attack and destroy cancer cells. BCG is used to treat early stage bladder cancer.
Toll receptor agonists are drugs that bind to Toll receptors and cause an immune response that destroys cancer cells. Toll receptors are found on the surface of most immune cells which can detect cancer cells and other germs in the body. When receptors detect cancer cells or germs, it tells immune cells to attack them. Imiquimod (Aldara) is a Toll receptor agonist sometimes used to treat early basal cell carcinoma, a type of skin cancer other than melanoma.
Immunomodulators strengthen the immune system, but we need to do more research to understand how they do this. Immunomodulators include the following drugs: thalidomide (Thalomid), lenalidomide (Revlimid), and pomalidomide (Pomalyst). It is used to treat multiple myeloma and some other types of cancer.
Receiving immunotherapy, How immunotherapy is done?, How is immunotherapy given?
Immunotherapy can be given in different ways: as a pill or capsule that you swallow (orally), through a needle in a vein (intravenously), or by application to the skin (topical).
Some immunotherapeutic drugs can only be given in hospital. Others can be taken at home.
Immunotherapy takes place according to a set schedule, or protocol, which is determined by your condition. Each treatment session usually consists of a treatment period followed by a recovery period.
Sometimes immunotherapy only is given, but it can also be combined with other types of treatment such as chemotherapy, radiation therapy or both.
How is immunotherapy given?
Different forms of immunotherapy may be given in different ways. These include:
Intravenous (IV): The immunotherapy goes directly into a vein.
Oral: The immunotherapy comes in pills or capsules that you swallow.
Topical: The immunotherapy comes in a cream that you rub onto your skin. This type of immunotherapy can be used for very early skin cancer.
Intravesical: The immunotherapy goes directly into the bladder.
Indications: for whom and what types of cancer?
To date, there are 9 specific immunotherapy drugs of this type. They can be used in many types of cancer, including lung cancer, kidney cancer, skin melanoma and forms of breast cancer, bladder cancer, ENT cancer (Head, neck, base of the skull, salivary glands and so on), Hodgkin’s disease, breast cancer… and should ultimately play a major role in the management of the majority tumors, including in the earlier stages.
Procedure: how does immunotherapy work?
The course of treatment differs depending on the type of immunotherapy used.
→ Treatment with monoclonal antibodies known as “checkpoint inhibitors”.
The treatment is administered in the hospital by infusion, mainly intravenously. The protocol depends on the molecule injected and the type of cancer, for example:
Ipilimumab is given intravenously over 90 minutes, followed by a 3 week rest period. The complete treatment includes 4 injections.
Pembrolizumab is administered intravenously over 30 minutes. The injection is given every 3 to 6 weeks, as long as the effectiveness of the treatment is observed with an acceptable tolerance.
Nivolumab is also administered intravenously over 60 minutes, every 2 to 4 weeks, as long as the effectiveness of the treatment is observed with an acceptable tolerance.
→ Treatment with CAR-T
These drugs are produced from the patient’s immune cells, his T lymphocytes. “They are therefore tailor-made drugs for each patient. First, the T lymphocytes are taken from them. They are then modified in the laboratory. which usually takes several weeks. The modified T lymphocytes are then administered to it “, explains Sophie Negellen. Only one intravenous administration of CAR-T is required. It takes place in the hospital. The patient first receives another chemotherapy which reinforces the expected effect of the treatment.
The treatments are aimed at very different pathologies. The same treatment will be very effective in a certain number of patients while it will be ineffective in others.
Side effects of immunotherapy
Regardless of the treatment, side effects may occur. Most of the side effects of immunotherapy are mild and go away once the body gets used to the medicine. If the side effects are severe, your doctor may stop treatment for a while or adjust the dose. The side effects of immunotherapy mainly depend on the following:
- the type of drug, drug combination or combination of treatments
- the dose
- the method of administration (by mouth or into a vein for example)
- your overall health
Everyone’s experience is different, but you may experience the following side effects.
Flu-like symptoms are a common side effect of immunotherapy. You may have a fever, chills, muscle and joint pain, nausea, vomiting, or loss of appetite (anorexia).
These symptoms often appear immediately after treatment. Giving the injection at bedtime and taking other medicines, such as acetaminophen (Tylenol), may help reduce them. You might even be able to sleep when they show up.
Flu-like symptoms usually go away during treatment, after the body gets used to the medicine. Check with your doctor or healthcare team if these symptoms do not go away or are bothersome.
Fatigue makes you more tired than usual and can interfere with daily activities and sleep. Fatigue is a common and temporary problem that can occur with some types of immunotherapy. It is often dose related and usually accompanies flu-like symptoms.
Find out more about fatigue.
Some immunotherapeutic drugs can cause a rash and itching. This can happen during treatment and may persist for some time after it is finished. Tell your healthcare team if you experience these skin changes. You may be offered moisturizers and creams and prescribed medications to relieve the itching.
Some people also have a skin reaction where the needle is inserted including swelling, redness, itching, rash and tenderness.
Immunomodulators called thalidomide, lenalidomide, and pomalidomide can cause serious birth defects if you are pregnant when you take them.
Report side effects
Be sure to mention your side effects to the healthcare team. Your team is there for you. Side effects can occur anytime during, immediately after, or a few days or even a few weeks after immunotherapy. Sometimes side effects may appear months or years after immunotherapy. Most go away on their own or can be treated, but some may last a long time or be permanent.
Immunotherapy concerns many other therapeutic areas
Immunity is involved in the control of many diseases and immunotherapy is already used in several areas:
Infectious diseases of course, with preventative vaccines that train the immune system to recognize and eliminate an infectious agent before a real infection occurs. This vaccination involves memory lymphocytes, which provide lasting protection for the vaccinated people. In addition, early trials involving immunomodulators have produced encouraging results against HIV. PD ‑ 1 inhibitory receptors have in fact been described on the surface of T lymphocytes in AIDS patients, and the removal of this inhibition by anti-PD ‑ 1 antibodies improves the antiviral response.
Allergic or autoimmune inflammatory diseases, corresponding respectively to the loss of control of the immune reaction upon exposure to an allergen or to cells of the self. Allergies are already treated by immunotherapy (desensitization), by accustoming the immune system to tolerate an allergen by gradual administration of the latter. The treatment of autoimmune diseases also involves modulation of the immune system, through immunosuppressants or monoclonal antibodies (anti-TNF alpha, anti-IL-1, anti-IL-6, anti-IL-12 / IL -23 …).
Neurodegenerative diseases, and in particular Alzheimer’s disease. Several recent trials have used monoclonal antibodies or therapeutic vaccination to promote the elimination of beta-amyloid peptide, unfortunately without success. But his work suggests a role for inflammation and immunity in the development of the disease. Targeting the immune system will probably become a new strategy to fight it.
The word “cancer” is a generic term for a large group of diseases that can affect any part of the body. We also speak of malignant tumors or neoplasms. One of the hallmarks of cancer is the rapid multiplication of abnormal growing cells, which can invade nearby parts of the body and then migrate to other organs. This is called metastasis, which is the main cause of death from cancer. Types of cancer (in alphabetical order of the area concerned):
Information: Cleverly Smart is not a substitute for a doctor. Always consult a doctor to treat your health condition.
Photo source: NIH Image Gallery / Flickr
Photo description: shown here is a pseudo-color scanning electron micrograph of an oral squamous cancer cell (white) attacked by two cytotoxic T cells (red), part of the natural immune response. Nanoresearchers are creating personalized cancer vaccines by loading identified neoantigens from patient tumors into nanoparticles. When presented with an immune stimulant, it activates the patient’s own immune system, leading to the expansion of tumor-specific cytotoxic T cells.
This image was originally submitted as part of the 2016 NCI Cancer Close Up project and was selected for exhibition.
Credit: Rita Elena Serda, Duncan Comprehensive Cancer Center at Baylor College of Medicine, National Cancer Institute, National Institutes of Health