Structure of the human antibody molecule with heavy chain in blue and light chain in red (IgG isotype shown)
Media Release: 05 February 2015
In today’s issue of Nature, a worldwide group of antibody experts appeal for a standardised approach to the creation and use of antibodies in research and therapeutics.
While it might cost roughly $US1billion to “generate characterized recombinant binding reagents to target the products of all human genes”, this would “probably be less than what is wasted worldwide on bad reagents in two or three years”, says Dr Andrew Bradbury from Los Alamos National Laboratory in New Mexico, the lead author of the opinion piece.
Associate Professor Daniel Christ, from Sydney’s Garvan Institute of Medical Research, is one of two Australian signatories. He believes that the current situation is very problematic because there is no quality control or standardisation in antibody production, making reproducibility of experiments difficult, and sometimes impossible.
“In many cases, the sequences that determine an antibody’s specificity have either not been defined or have not been made publicly available,” said Associate Professor Christ. “I think it would be desirable if the sequences of antibodies were deposited online, and made accessible to the wider community.”
Millions of antibodies are used in research – often coupled to dyes or fluorescent chemical compounds – to allow scientists to track molecules of interest. The signatories of the Nature opinion piece believe that antibodies should be predominantly produced as ‘recombinant’ proteins, using defined sequences and conditions, allowing researchers worldwide to use identical reagents.
At present, many research labs use ‘hybridomas’, created by fusing an antibody-producing cell with a cancer cell. “Hybridoma cell lines can die off, lose their antibody genes, or simply not grow when taken out of frozen storage — meaning that the source of a particular monoclonal antibody may be lost forever,” said the opinion piece.
The authors therefore call on the public funding agencies of the world’s largest economies – the United States, Europe and Asia – to fund the transition to recombinant antibodies. “Publishers and funding agencies should mandate that, in say five years time, all binding reagents in published papers are recombinant and defined at the sequence level," they said.
“This would mirror the requirements for the past few decades that gene sequences and coordinates for new protein structures be deposited and made publicly available.”
Led by Professor Christ, the Garvan Institute has established the Centre for Targeted Therapy to focus on quality control of reagents and the development of therapeutic antibodies.
“We are putting a lot of effort into maintaining specialist staff and equipment essential for antibodies characterisation,” said Christ.