Monoclonal antibody therapy

Monoclonal antibody therapy is the use of monoclonal antibodies (or mAb) to specifically target cells.

The main objective is stimulating the patient’s immune system to attack the malignant tumor cells and the prevention of tumor growth by blocking specific cell receptors.

Variations exist within this treatment, e.g.radioimmunotherapy a radioactive dose directly to the target cell, and lethal chemical doses to the target. Structure and function of human and therapeutic antibodies Immunoglobulin G (IgG) antibodies are large heterodimeric molecules, approximately 150 kDa and are composed of two different kinds of polypeptide chain, called the heavy (~50kDa) and the light chain (~25kDa).

There are two types of light chains, kappa (κ) and lambda (λ).

By cleavage with enzyme papain, the Fab (fragment-antigen binding) part can be separated from the Fc (fragment crystalline) part of the molecule. The Fab fragments contain the variable domains, which consist of three hypervariable amino acid domains responsible for the antibody specificity embedded into constant regions.

There are four known IgG subclasses all of which are involved in Antibody-dependent cellular cytotoxicity. The immune system responds to the environmental factors it encounters on the basis of discrimination between self and non-self.

Tumor cells are not specifically targeted by one’s immune system since tumor cells are the patient’s own cells.
Tumor cells, however are highly abnormal, and many display unusual antigens that are either inappropriate for the cell type, its environment, or are only normally present during the organisms’ development (e.g.fetal antigens). Other tumor cells display cell surface receptors that are rare or absent on the surfaces of healthy cells, and which are responsible for activating cellular signal transduction pathways that cause the unregulated growth and division of the tumor cell.

Examples include ErbB2, a constitutively active cell surface receptor that is produced at abnormally high levels on the surface of approximately 30% of breast cancer tumor cells. Such breast cancer is known a HER2 positive breast cancer. Antibodies are a key component of the adaptive immune response, playing a central role in both in the recognition of foreign antigens and the stimulation of an immune response to them. The advent of monoclonal antibody technology has made it possible to raise antibodies against specific antigens presented on the surfaces of tumors.