Biologists have created two lines of goats that produce anti-cancer antibodies cetuximab with milk. Transgenic goats will help to reduce the cost of production of the drug and increase productivity. In addition, cetuximab isolated from milk has advantages over the commercial drug, which is used now: he runs more effective cytotoxic response, and is not responsible or immunogenic epitope. A Preprint of the article is available on the portal bioRxiv.
Monoclonal antibodies used as drugs in a number of diseases, including various cancers. Antibody production based on cell cultures of mammals in such conditions the recombinant proteins correctly glycosylases that it is often necessary for their work. However, the cell culture are costly and inefficient production method.
Alternatively, cell cultures use the milk of transgenic animals together with the milk they produce the necessary proteins. This approach is much cheaper and allows to produce recombinant substances in large volumes. Milk goats are already getting human antithrombin, and rabbits — inhibitor C1-esterase and factor in blood clotting VII.
Scientists from New Zealand, USA and France under the direction of Goetz Laible (Götz Laible) from the Research center in Ruakura created transgenic goats in milk which stood cetuximab — monoclonal antibodies to receptor of epidermal growth factor, which is used to treat colorectal cancer and cancer of the head and neck.
In embryonic fibroblasts goats introduced genetic constructs that encode the two chains of the cetuximab (heavy and short). The kernel of the nine cell lines that have been successfully produced antibodies transferred to eggs of goats (the same procedure is carried out when cloning) of them raised kids. When they grew up, they hormone stimulated the secretion of milk, it analyzed the number of light and heavy chains of cetuximab.
Of the nine lines of transgenic goats, only two produced enough milk for 30 days of hormone stimulation. In the milk of goats of these lines confirmed expression of both active circuits cetuximab, 100 milliliters of milk one of the goats was able to extract 850 mg of pure antibodies. The descendants of the first, second and third generations of goats carrying the same number of copies of transgenic alleles as founders of the lines, and antibodies with the milk.
Cetuximab isolated from milk was tested on cell lines breast cancer person, which Express the drug target — the receptor of epidermal growth factor. Antibodies from milk was associated with the receptor is not worse than the commercial drug “Erbitux”, which produced cell culture. Moreover, cetuximab produced goats, better Erbitux interacted with the receptor CD16 (he plays a key role in antibody-mediated cytotoxicity) and, thus, can better withstand the cancer cells. The reason for high efficiency binding, scientists believe, was different glycosylation of the protein in the cells of goats.
Glycosylation analysis showed that cetuximab of the milk is not of the epitope α-Gal, which is in Erbitux and triggers the adverse immune reaction. This could be another advantage of the antibodies produced by goats, but it is necessary to conduct additional investigation for detailed comparison of the properties of the two drugs.
Another unusual method of production of drugs using a 3D printer. So I tried to print tablets of paracetamol — the procedure did not affect the stability of the substance, and pills in the shape of pyramids dissolve faster than normal cylindrical.