The innate immune system
Unlocking the body’s natural
antibody repertoire
The innate immune system is the body’s first mechanism of defence, harnessing physical barriers and non-specific pathways to rapidly clear foreign pathogens. Alphamers® enable us to combat disease or infection by exploiting elements of this immune response, even in vulnerable patients where other approaches are ineffective.
History
Pioneering work into xenotransplantation in the 1960’s gave us the first insights into anti-glycan antibodies, and the immune response they can elicit. In these studies, transplanted tissues from animal species were rapidly rejected in humans. Further work revealed this was due to the presence of alpha-gal glycans in the transplanted tissue – molecules expressed in all mammalian species except humans, apes, and old-world monkeys.
Anti-glycan antibodies are known to be present in humans due to exposure in the gut. They are ubiquitious, high-titre, and polyclonal, existing as both IgM and IgG subtypes within our natural antibody repertoire.
Anti-glycan antibodies
We now understand that this immune response is not limited to alpha-gal glycans, and research has uncovered additional antibodies, such as anti-rhamnose, which share similar properties.
These naturally existing antibodies have low affinity but high avidity, meaning that only densely populated glycan epitopes elicit an immune response. We are able to exploit this avidity with our Alphamer® technology, allowing us to precisely direct the host immune response to a disease target.
Once bound, anti-glycan antibodies trigger a broad innate immune response through engagement with multiple immune effector pathways, including complement activation and phagocytosis via neutrophils and macrophages. Crucially, this mechanism has been shown to be effective even in seriously immune-compromised patients where other treatments may not be suited.
