From HAMIGA™ technology to therapeutic approaches
The originality of B Cell Design's therapeutic projects lies in the role of IgA in mucosal immunity and as an aid in the fight against mucosal pathologies (infectious diseases whose point of entry is the mucosal barrier, cancers, chronic inflammation, etc.). B Cell Design has opened up a wide range of applications for the development of future therapies.
B Cell Design technology: HAMIGA™
Hamiga™ is a patented transgenic mouse for the generation of human chimeric IgA antibodies. In a normal animal, less than 1% of B lymphocytes in the spleen express IgA antibodies. It has therefore long been difficult to isolate and produce specific monoclonal IgA for basic research to explore its potential therapeutic benefit. HAMIGATM technology has removed the technology barrier, with more than 60% of splenic B cells expressing human chimeric IgA and almost 99% of hybridoma cells generated through the HAMIGA™ platform expressing human chimeric IgA1. The HAMIGA™ platform generates a wide range of specific monoclonals (mAbs) targeting a variety of antigens. These mAbs can be sorted according to their characteristics (stability, antibody production rate, etc.) and/or functional criteria (cell growth inhibition, neutralization, apoptosis induction, recruiting of human effector cells, etc.). The HAMIGA™ platform is used to develop and select the best clone among thousands of clones in the application of interest.
The main difference between HAMIGATM technology and a traditional antibody humanization process by genetic engineering is the speed with which a chimeric antibody of interest may be generated. Up to now, B Cell Design has already developed dozens of specific IgA1 targeting different kinds of antigens as part of internal developments or in partnerships with academic partners and manufacturers.
The innovation: a mucosal vaccination
Secretory IgAs could be used as a vector to transport protecting epitopes within lymphoid tissues in the mucous membranes and trigger a neutralizing immune response. (Corthesy et. al) Secretory IgAs are able to translocate antigens from the lumen to the lamina propria where they are addressed to dendritic cells.
The oldest demonstration is illustrated by the immunity acquired by babies from mothers. IgAs are transmitted to the baby through direct contact with the mother’s mucous membranes and through the milk. The baby’s immune system is trained and therefore more resistant to various diseases.
The mucosal vaccination concept is based on secretory IgA’s ability to cross the mucosal barrier, from lumen to lamina propria, to carry new epitopes and locally stimulate the whole immune system. SIgA may also translocate microorganisms, alive or attenuated, which could be a new route for administering a vaccine and a new way of inducing a protective response.