This (Glycart) looks interesting (IMGN shareholders might find it disturbing):
chi-peptalk.com
9:20 Cell Line Engineering for Production of Therapeutic Antibody Glycoforms with Increased Biological Activity
Dr. Pablo Umaña, Chief Scientific Officer, GLYCART Biotechnology AG (Swizerland)
Controlling and manipulating protein glycosylation is becoming increasingly important with respect to the development of biotherapeutics. This talk will cover the topic of introducing genetic modifications for stable overexpression of glycosyltransferase genes in antibody production cell lines. Several antibodies have been engineered using this approach, and biological activity (ADCC) increases of at least two orders of magnitude have been obtained for a chimeric anti-CD20 and anti-EGFR antibodies, unmodified versions of which are already in the market or in the clinic....
from the website
GlycoMAb works by genetically engineering the antibody-producing cells with a gene encoding an oligosaccharide-modifying enzyme (a particular glycosyltransferase). The modified cells produce new molecular variants of the antibody, bearing special types of oligosaccharides attached to the antibody constant region. These are called glycosylation variants of the antibody, making GlycoMAb a glycosylation engineering approach. The special types of oligosaccharides (called "bisected non-fucosylated" oligosaccharides) are not made by the standard cell lines used for antibody production in the biotechnology and pharmaceutical industries.
Antibodies produced using GlycoMAb are highly enriched (at levels much higher than those found in nature) in these bisected non-fucosylated glycosylation variants. The modified antibodies engage more efficiently immune effector cells in killing undesirable antibody-targetet cells, leading to a large increase in specific antibody activity...
Features & Benefits
1. By genetically modifying the antibody-producing cell line, very large increases in potency of whole antibodies are obtained while maintaining a simple production process that lacks chemical-conjugation and extra purification steps.
2. Efficient and robust glycosyltransferase gene-expression vectors have been constructed for this purpose. The genetic modification is rapidly implemented via standard procedures widely used in industry for the generation of cells lines producing commercial therapeutic proteins (including antibodies).
3. Equally, the stability of GlycoMAb-modified cell lines is tested in the standard and reliable way used for all commercial recombinant protein-producing cell lines. Similarly, standard procedures for antibody product quality control are applicable. In summary, no new steps, reagents, equipments, personnel, costs or risks are added to the antibody production process.
4. GlycoMAb conserves the bivalent target-binding nature of antibodies and does not use toxic, immunogenic or radioactive moieties that can lead to higher side effects, elevated production costs or complex logistics from production to administration to patients.
5. GlycoMAb can be applied to industrial antibody-production cell lines without affecting specific antibody productivity or cell growth (in suspension in serum- and protein-free cell culture medium).
6. In addition to our GlycoMAb gene-expression vectors for the engineering of antibody-producing cells, GLYCART has established various GlycoMAb-modified "empty" cell lines with fully traceability. The cells are already glycoengineered, are pre-adapted to growth in suspension in protein-free medium, and are ready for the generation of GlycoMAb-based antibody-producing cell lines... |
