A new way of mass-producing cancer drugs has been shown to also improve their effectiveness in work published this month by a collaboration between Against Breast Cancer scientists at the University of Oxford and in Germany.
Currently, human cell lines are used to produce almost all commercially available antibody treatments in order to ensure that they have human-like properties. This prevents the body being stimulated to generate an immune response against the treatment itself (which would prevent the treatment from working), but using human cell lines is a timely and costly process that can be unstable and affected by contamination. Cheaper, alternative production systems e.g. using insect or yeast cells, have been investigated to yield high quantities of a drug without compromising on quality, but with limited success.
Comparison of the sugar forms on antibodies produced using different systems
Scientists in Germany from the University of Münster, Pharmaanalytik Münster and a company called Cilian AG, who own the technology, used a fast-growing water-borne, single-celled organism called Tetrahymena thermophile, commonly called a ‘ciliate’, to produce anti-cancer antibodies. They were able to demonstrate large-scale production but when it came to testing the antibodies, they were surprised at how well they worked compared to antibodies produced using human cell lines. To understand the mechanisms behind this improved effect, expert biochemists were called in to investigate.
Dr. Max Crispin, one of the authors of the study, is head of the Oxford Glycoprotein Therapeutics Laboratory and the recipient of the Against Breast Cancer Research Fellowship.
His group looked at the arrangement of sugar molecules found on the surface of antibodies produced in each system, and compared how each of the antibodies functioned against cancerous cells. They discovered an unusual sugar form on the ciliate-produced antibody that was able to mimic the human form, which enabled the antibodies to recruit cells of the immune system and direct them to kill off cancerous cells more effectively than the commercially-available antibody performed.
The research was published in the international journal mAbs (Monoclonal Antibodies).