Harnessing the immune system's arsenal: producing human monoclonal antibodies for therapeutics and investigating immune responses

Sullivan, Meghan; Kaur, Kaval; Pauli, Noel; Wilson, Patrick C.

Monoclonal and polyclonal antibodies as therapeutics: from humble beginnings Modern antibody treatments are rooted in classic experiments performed in 1890 by Emil von Behring and Kitasato Shibasaburo. Their experiments were the first to bring to light that effective "antitoxins" to pathogens such as tetanus and diphtheria could be generated in serum by immunizing animals with bacterial lysates [1] . The use of antitoxins generated in animals was such a major advance in the treatment of a wide range of infectious diseases that it earned a Nobel Prize for von Behring in 1901. However, serum harvested from animals contains a diverse mixture of antibodies, including those with irrelevant binding specificity or those that bind the pathogen but do not lead to its removal or neutralization. Such mixtures are polyclonal, meaning they are comprised of many different antibodies binding a variety of epitopes and are produced by many different B cell clones. Because of the heterogeneous and unpredictable composition of polyclonal antibodies, technologies targeted at producing homogenous monoclonal antibodies have undergone rapid development and advancement. The very concept of monoclonal antibodies was not truly realized until work in the 1950s by Frank Macfarlane Burnet and David W. Talmage [2, 3] . Their work culminated in a model of how our immune systems function known as the theory of clonal selection, which included the central tenant of modern immunology: that each lymphocyte recognizes a single molecular target or epitope via a unique receptor. This observation naturally led to the idea that monoclonal antibodies arising from a single B cell clone and recognizing the same epitope could be a valuable and informative resource. Later generations of scientists developed technologies to exploit the "one B cell, one antibody" dogma to generate monoclonal antibodies. Since the 1950s, a number of monoclonal antibodies have been patented as treatments and effective diagnostics.