Hapten engineering: Raising antibodies against the smallest of small molecules

Approximately 10 million different molecules could be regarded as haptens. Of these, at least 200 000 are man-made, and include drugs, pesticides and industrial chemicals. Biological organisms also synthesize and make abundant use of haptens for a host of activities, for example, as antibiotics, toxins and hormones, and as part of a plethora of related signalling systems. As with all antigens, the specificity and sensitivity of anti-hapten antibodies can be a significant issue, particularly when considering their administration as therapeutics. Depending on the application, cross-reactivity with related molecules could be either of benefit or a distinct disadvantage. Through the careful design of antigens and the use of appropriate antibody-isolation strategies, human antibodies The human immune system is primed to react to infection events, typically initiated by bacteria, viruses or larger-molecular-mass proteins derived from these organisms. Evolution has honed the body’s defences to counter these relatively large intruders, but smaller molecules are overlooked and circulate freely. Indeed, many current drugs function in vivo because they are small enough to evade the immune response. As a consequence of this evolutionary process, the raising of antibodies to proteins (even human antibodies) is now relatively straightforward. In contrast, the isolation of antibodies that recognize smallermolecular-mass antigens (typically below 1500 Da, and often referred to as haptens) has remained a significant technical challenge. that are fully cross-reactive or do not cross-react at all with related molecules, can be selected and isolated. This is often possible, even when molecules differ by as little as a single methyl group. However, the approach is not limited to the isolation of antibodies to small-molecular-mass targets (haptens). Recently, the isolation of human antibodies specific for the molecular signature (haptenic structures) of larger-molecular-mass targets, such as polymers, peptides, modification-state proteins, glycoproteins, bio-toxins and a number of cell-surface antigens, has been undertaken. In general, the strategy (termed HaptomicsTM) works well for targets considered difficult or beyond the reach of current antibody approaches. One of Haptogen’s current research interests is a group of haptens involved in the complex process of cell-to-cell communication. This occurs in all organisms, both single-celled and multicellular and the transfer of information through the movement of haptens, as illustrated by ligand–receptor binding, is one of the most frequently used routes by which cells communicate with each other. Researchers have long targeted these pathways in an attempt to gain therapeutic benefit. Competing concentrations of mimetic drugs are administered to interfere or block ligand–receptor binding. In drug discovery terms,