Antibodies are proteins used by the immune system to identify and neutralize foreign bodies, such as bacteria, viruses, or tumor cells. An antibody recognizes a specific target, the so called ‘antigen’, which is present in cells that were noticed as foreign by the host organism. Each antibody has two sites available, called paratopes, which link to a specific part of the antigen, the epitope. The specificity that determines the affinity between antibodies and antigens is similar to that between locks and keys. This interaction signals a response that activates other components of the immune system to destroy, for example, microorganisms or tumor cells. Antibodies belong to a class of proteins known as immunoglobulins, which are produced and secreted by B lymphocytes in response to stimulation by antigens.
Monoclonal antibodies (mAbs) are antibodies produced by a single clone of a parent B lymphocyte, and, therefore, are identical in relation to their physicochemical and biological properties. Antigen-specific mAb populations can also be generated in laboratory, in order to recognize and bind to any antigen of interest. Such a procedure was described for the first time in 1975, in an article published in the magazine Nature by the scientists Cesar Milstein and Georges Köhler. For their feat, both shared the Nobel Prize for Medicine in 1984 with the Danish Niels Kaj Jerne.
Monoclonal antibodies are produced in the laboratory starting from B lymphocytes generated in mice, whose immune systems have been stimulated by antigens of interest. These antibodies are called ‘murine antibodies’. However, due to their murine origin, these antibodies can induce an anti-mouse antibody immune reaction in the human body, if used repeatedly. For this reason, the use of mAbs remained limited for two decades to the production of kits for diagnosis and scientific research.
However, modern genetic engineering techniques have allowed investigators to ‘humanize’ antibodies; that is to say, the genes responsible for the production of these proteins have been modified to eliminate the body’s anti-mouse antibody immunological reaction. The process of humanization must not alter the antibody’s affinity towards the respective antigen, enabling so its continued application in therapeutic procedures.
In the area of oncology, a new generation of medicines is being developed based on the capacity of mAbs to recognize specific tumor antigens and to induce an immune response against the cancerous cells. In addition to this, mAbs can be modified to act as carriers of radioactive isotopes or toxins to cancerous cells, amplifying their spectrum of therapeutic application.
Currently, there are few mAbs approved for therapeutic use against neoplasias (in 2011, only 10). There are, nevertheless, a large number of mAbs under investigation by research institutes and biotechnology companies throughout the world, for this same purpose. In Brazil, RECEPTA has already initiated its development project involving mAbs with tremendous potential for cancer treatment. This development effort includes immunohistochemistry analyses, pre-clinical studies and clinical trials (Phases I and II) being conducted within Brazil.