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Antibodies are immunoglobulins, i.e. proteins with immune functions. Immunoglobulins are categorized into five classes, which identify their structural makeup and the types of immune responses produced: immunoglobulin G (IgG), IgD, IgA, IgM, and IgE. IgG is the most common immunoglobulin in the body, whereas IgE makes up less than 1%.² The human body produces antibodies via B cells to attack and destroy antigens. Antigens are foreign substances that the body identifies as invasive and requiring removal. In individuals with autoimmune diseases, such as rheumatoid arthritis or lupus, the body incorrectly identifies itself as being foreign and will attack its own cells. Augmenting this misaligned process can produce clinical benefit and is a target for biological drugs.²

There are two predominant ways to classify antibodies based on their source and how they are harvested: polyclonal antibodies and mAbs. As the name suggests, polyclonal antibodies contain many (‐poly) antibodies; not only the desired antibody to be used for a clinical effect, but also unwanted antibodies that the immune system may see as foreign. Polyclonal antibodies can be derived from horse blood samples (botulism antitoxin, diphtheria antitoxin, tetanus antitoxin), or from human donors (hepatitis A and B immunoglobulins, or immunoglobulin for measles, rabies, and tetanus, respectively).²

In this process, an antigen (foreign matter) is injected in an animal, then the animal develops an immune response mediated by B cells and produces antibodies. The antibodies are harvested and packaged for later clinical use in humans. This type of antibody development has been in existence for decades, but not without its problems. In 1901, a batch of the diphtheria antitoxin became infected with tetanus resulting in the death of 13 children. Subsequently, in 1902, the United States passed The Biologic Control act, which was meant to ensure the safety of biologics and was the predecessor of the FDA's Center for Biologics Evaluation and Research (CBER), which exists today.¹²

mAbs were developed in the 1970s and as the name suggests, would lead to the harvesting of only one (‐mono) type of antibody, which leads to more specificity for antigen binding. mAbs are typically produced by injecting a mouse with antigens, resulting in the mouse developing an immune response mediated by B cells. At this point, the B cells are removed and fused with myeloma cells, resulting in what is called a “hybridoma.” Myeloma cells are used for their long lifespan and ability to replicate, like cancer cells. This allows mAbs to be produced continuously resulting in an efficient manufacturing machinery. Since mAbs are still produced from animal, the potential for allergic reaction or neutralization by the human body exists.²

Advances in science allowed for mAbs to become more humanized over time; first with chimeric antibodies that contained mouse and human proteins (an example is the drug, Reopro^®), then with humanized antibodies that further minimized the components made from mice (e.g. Herceptin^®), and finally, fully human antibodies (e.g. Humira^®, the first fully human antibody approved by the FDA). Antibodies can also be conjugated with other products such as small molecules or radiopharmaceuticals that use the specificity of the antibody‐to‐antigen to target a site and then release a secondary pharmaceutical agent for therapeutic purposes.²

The future of mAbs development may include bi‐specific antibody development, meaning antibodies that possess two binding specificities. This could be advantageous as targeting multiple targets simultaneously could inhibit various receptor‐ligand signaling pathways more effectively and limit development of disease‐cell resistance. In 30 years since the first therapeutic mAb was approved in 1986, there are more than 294 mAbs being used clinically, with almost 90% of them being humanized mAbs with the remainder being chimeric mAbs.¹³