Generality
Immunotherapy is a method for treating pathologies based on the use of substances that act on the immune system.
- Suppression immunotherapy : when you want to depress the response of the immune system. Suppression immunotherapy is used, for example, to treat allergies, in which the body is hypersensitive to certain external agents (antigens). The purpose of immunotherapy, in this case, is to limit the excessive immune reaction that triggers in response to contact with the antigen; in this way a desensitization of the organism towards the agents triggering the allergy is obtained.
Other circumstances that make it appropriate to use suppression immunotherapy include organ transplants, to prevent rejection, and the treatment of autoimmune diseases.
- Activation immunotherapy : in this case, the purpose of immunotherapy is to induce or amplify an immune response. This is the case of antimicrobial immunotherapy - including vaccines against infectious agents - and of oncological immunotherapy, ie of the immunotherapy used in the treatment of tumors.
Activation immunotherapy can also be used in case of immunodeficiency, caused by pathologies (for example, AIDS) or iatrogenic origin (side effect of other treatments, such as chemotherapy or radiotherapy).
Oncological immunotherapy
Oncological immunotherapy uses the immune system to treat tumors.
The cells of our body expose on their surface molecules of different nature, such as proteins and carbohydrates.
Malignant cells - as a consequence of the mutations that led to the development of the tumor - expose, on their surface, molecules different from those exposed by healthy cells. These molecules are called tumor antigens . Oncological immunotherapy exploits precisely this phenomenon: the cells of the immune system may be able to identify tumor antigens and attack the diseased cells that expose them.
Oncological immunotherapy can be divided into three main groups:
- cell therapy;
- antibody therapy;
- cytokine therapy.
Cell therapy
Cell therapy involves the administration of so-called cancer vaccines . Usually, immune cells are taken from cancer patients, both from the bloodstream and from the tumor itself. Once taken, the immune cells are activated in a way that specifically recognizes the tumor cells, then cultured in vitro and finally returned to the patient. In this way, once returned to the body, tumor-specific immune cells should be able to identify and attack it.
The types of immune cells that can be used in cellular immunotherapy are dendritic cells, natural killer cells, cytotoxic T lymphocytes and killer cells activated by lymphokines .
To date (April 2015), only one vaccine for cellular immunotherapy has been approved against cancer in Europe; the drug is called Provenge ® and is used in the treatment of advanced prostate cancer. Many other vaccines are being researched and studied, while some are already in an advanced clinical trial phase.
Antibody therapy
Antibody immunotherapy is undoubtedly a consolidated and widespread therapy for the treatment of tumors.
Antibodies are proteins with a particular "Y" shaped structure, which originate from cells of the immune system called plasma cells . In correspondence of the short arms of the "Y" there are specific areas able to recognize numerous types of antigens. When an antibody recognizes an antigen, they interact with one another with a sort of " key-lock " mechanism. In particular, it can be said that each antibody has a "lock" (placed on the short arms of the "Y") to which corresponds a specific "key" (antigen). When the antigen-antibody interaction occurs - so when the key is "inserted" - the antibody becomes active, initiating the cascade of biochemical signals that leads to the body's immune response.
In normal physiological conditions, the antibodies of the immune system are mainly used for the recognition of pathogenic microorganisms. However, there are antibodies that can recognize tumor antigens and therefore can be used in the treatment of tumors.
In antibody immunotherapy monoclonal antibodies ( mAbs ) are used, so called because they are clones coming from cell lines deriving from a single immune cell.
Once the antigen of interest is identified, it is possible to create - thanks to specific techniques - monoclonal antibodies that are specific for that antigen.
Below are some of the monoclonal antibodies used to treat cancer.
- Alemtuzumab, given intravenously, is used to treat chronic lymphocytic leukemia.
- Bevacizumab, used in combination with other anticancer drugs for the treatment of metastatic colorectal cancer, advanced or metastatic lung cancer, metastatic carcinoma of the breast and advanced or metastatic carcinoma of the kidney. It is given intravenously.
- Cetuximab, given by intravenous infusion, is used to treat metastatic carcinomas of the colon and rectum and head and neck carcinomas.
- Ibritumomab tiuxetan (Zevalin ®), this monoclonal antibody is conjugated with the radioactive yttrium 90 isotope. It therefore combines the activity of the antibody with that of the γ rays produced by the radioisotope. He was the first agent to become part of radioimmunotherapy . It is used in the treatment of non-Hodgkin's lymphomas and is given intravenously.
- Ipilimumab, used in the treatment of advanced melanomas, administered by drip into a vein.
- Panitumumab is administered intravenously and is used in the treatment of metastatic colorectal cancer.
- Rituximab, used in the treatment of non-Hodgkin's lymphoma and chronic lymphocytic leukemia; it is also used for the treatment of rheumatoid arthritis. It is given by intravenous infusion.
- Trastuzumab, used for the treatment of breast cancer; it is found as a powder that is solubilized so as to administer it by intravenous infusion.
Cytokine therapies
Cytokines are polypeptide mediators, that is, they are proteins responsible for communication between the various cells that make up the immune system, and between immune cells and other tissues and organs.
Some cytokines are produced by cells of the immune system and can be used in oncological immunotherapy, such as interleukin-2 and interferon-α.
Interleukin-2 is used in the treatment of melanoma, kidney cancer and acute myeloid leukemia.
Interferon-α is used for the treatment of hairy cell leukemia, chronic myeloid leukemia, multiple myeloma, follicular lymphoma and melanoma.
Side effects
The side effects that can be caused by immunotherapy are due to the hyperactivity of the immune system. Indeed, it may happen that the immune system attacks, not only the sick cells, but also the healthy ones because it is no longer able to recognize them as such.
The side effects, however, may vary depending on the type of immunotherapy and depending on the drug being administered. The most common effects can be:
- Fatigue;
- Itching and redness;
- Nausea and vomit;
- Diarrhea;
- Colitis;
- Increased transaminases (enzymes present in the body that are often used as an index to detect the presence of liver damage);
- Altered functioning of endocrine glands, especially thyroid and pituitary glands.
Despite the side effects that can occur, the strong point of immunotherapy is that it does not use drugs that directly target cancer cells, but instead uses molecules and cells from the immune system that are naturally part of the body.
Lymphocytes (the cells that make up the immune system) can selectively attack malignant cells, considerably reducing the tumor mass. Immunotherapy could make it possible to treat unresectable tumors and thus increase average survival.
Because of the hopes it offers, clinical trials and trials using immunotherapy for the treatment of numerous types of tumors are underway.
