Dr Daniel Christ
28 November 2013
Garvan immunologist Dr Daniel Christ has been recognised by the National Health and Medical Research Council (NHMRC) as one of the top-ranked applicants in the 2012 round of grant and fellowship awards. (See the NHMRC media release.)
Last night Dr Christ received his Excellence Award at the Academy of Science in Canberra. The award winners represent the top 20 out of 5236 peer reviewed applicants for funding in 2012.
Dr Christ received his award in recognition of his NHMRC Fellowship ranking (CDF2 category) and the contribution he has made towards biotechnology and development of monoclonal antibodies.
Monoclonal antibodies are highly targeted therapies against cancers and inflammatory conditions, such as rheumatoid arthritis. They represent about half of all candidate molecules entering clinical trials, with several new drugs being released each year.
Dr Christ heads an Antibody Therapeutics group at Garvan, which recently overcame one of the most pressing problems in the pharmaceutical industry by creating antibodies that are not only full human, but also stable and resistant to aggregation.
“When you take these molecules out of their natural environment, purify and concentrate them, stresses become apparent,” said Dr Christ.
“As a drug, antibodies are formulated at very high concentrations, for instance for delivery in a small syringe. Under these conditions, they can stick to surfaces like tubing and become entangled with one another.”
“In our lab, we developed specific mutations that universally increase the stability of the antibody molecule, making it much less sticky, much less entangled. The mutations also make the antibodies more robust during storage.”
“There are currently around 35 antibodies in the clinic worldwide, and over 500 antibodies in clinical studies, a massive recent increase, making antibody stability a critical issue.”
“All these antibodies will ultimately have to be manufactured, and that is not trivial because between 30-50% of these molecules have issues with stability”.
“By the time you go into early manufacturing or clinical studies, you may have invested 20 or 30 million dollars into a candidate molecule. If a large proportion of these were to fail because of limited stability, it would be a complete disaster.”
“My lab over many years has been working at developing long-term rational approaches where we look at the basic structural and physical principles underpinning the stability of the antibody molecule”.
“In other words, we aim to find general solutions that work, maybe not for every antibody, but a large proportion of the antibody repertoire. So if someone comes to us with a problem, we can offer general solutions, tools and pathways towards more stable variants.”
“The work is progressing very nicely, and is something we have been increasingly carrying out in collaboration with industry.”