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.

Recently, the business of producing monoclonal antibodies has undergone yet another technological advancement-recombinant human monoclonal technology, or "expression cloning." A rather new addition to existing technologies, expression cloning is the production of fully human monoclonal antibodies by isolating single B cells from human blood and expressing their antibody genes in vitro. This approach was first used on a large scale by the Nussenzweig laboratory and alumni to explore human B cell selection and tolerance (for example, see [23] [24] [25] , amongst a number of other papers). This powerful method requires only hundreds of B cells and allows for the production of antibodies that are natural (fully human) from highly discrete subsets of B cells that have become specialized within the body. A significant advance in applying this approach occurred when it was realized that antibody genes from antibody-secreting cells, activated during ongoing immune responses to vaccinations or infections, could be isolated and then cloned to generate an unprecedented number of antigen-specific and fully human mAbs in a short time span [26] [27] [28] . Furthermore, these heavy-and light-chain-encoding genes are transfected into mammalian cell cultures, which ensures that they receive appropriate post-translational modification such as glycosylation, a factor that influences specificity and the monoclonal antibody's ability to be tolerated by a human recipient. This is especially relevant as glycosylation is lost in nonmammalian culture conditions, such as those used for phage display.