Talk of Peter Hermentin

On the 23th of July, the iGEM Marburg got the opportunity to attend a lecture of Dr Peter Hermentin, a former inventor at Behringwerke AG in Marburg. In his short introduction he pointed out differences between diagnostic and therapeutic antibodies. Whereas diagnostic antibodies are comparatively cheap and usually free of any patents, therapeutic antibodies are quite expensive and, in most cases, patent-protected. Following this, he gave us some general information concerning the principles of operation and application of therapeutic antibodies, e.g. that therapeutic effects are generated in the Fc-Region of the antibody. As an example of use, he taught us the antibody-labeling of tumor cells. This targeting of tumor antigens may lead to cross-links between antigens followed by apoptosis of tumor cells. Other consequences might be the attraction of macrophages und native killer cells and the creation of contact points for the complement system which is part of our immune system. The accurate effectiveness of an antibody depends on its glycosylation pattern whereupon the core region may appear similar to:

As a general problem regarding the antibody production in non-mammals like plants and especially microalgae Mr Hermentin advised us of different glycosyltransferases used in this species that create glycosylation patterns that are not biocompatible to humans.

To accomplish his lecture, he presented a possibility to avoid this problem in our organism Phaeodactylum tricornutum. Interestingly, Phaeotory provides all enzymes required for N-Glycan biosynthesis in its ER and Golgi complex. Additionally, 'P. tricornutum' is capable to build high-mannose structures. Unfortunately, the organism uses two glycosyltransferases, α(1,3)-Fucosyltransferase and β(1,2)-Xyloysltransferase, that are not compatible to humans. This means that the production of therapeutic antibodies in 'P. tricornutum' for human application demands the knockout of these two genes.

For further information check out these two articles:

[1] Baiet B, Burel C, Saint-Jean B, Louvet R, Menu-Bouaouiche L, Kiefer-Meyer MC, et al. N-glycans of Phaeodactylum tricornutum diatom and functional characterization of its N-acetylglucosaminyltransferase I enzyme. J Biol Chem. 2011, 286(8), 6152-64.

[2] Bowler C, Allen AE, Badger JH, Grimwood J, Jabbari K, Kuo A, et al. The Phaeodactylum genome reveals the evolutionary history of diatom genomes. Nature. 2008, 456(7219), 239-44.