Separating the wheat from the chaff in antibody research
the interactions between an antibody-based drug and the proteome -
a snapshot of all the proteins produced by a cell.
Although the study looked at a microarray covering the proteome of a yeast cell, the lessons learned could equally be applied to humans using human proteome arrays. And this could help accelerate development of medical, diagnostic and research antibodies, and offer the potential to significantly improve the speed and success rates of innovative antibody-based drugs.
The approach maps out which cellular proteins - out of the thousands that are present in a cell - are affected by the antibody. This allows researchers to build up a precise picture of the cellular functions that will be affected by the antibody and in turn, guide the selection of the best candidate to take forward in development.
The study, reported in the December issue of Nature Biotechnology, describes the detailed interaction of publicly-available polyclonal and monoclonal antibodies targeted at specific yeast proteins.
Using Protometrix' Yeast ProtoArray, which is made up of more than 4,000 unique proteins representing a majority of the proteome of the yeast Saccharomyces cerevisiae, investigators demonstrated that a number antibodies thought to be specific for a unique protein actually cross-react with tens to hundreds of unanticipated proteins.
This provides "unprecedented knowledge about antibody specificity, a key factor in determining the likelihood that an antibody may trigger an undesirable biological response or may generate misleading experimental test results," said Paul Predki, the company's vice president of research.
"Our results using the Yeast ProtoArray imply that similar studies on human proteome-scale microarrays will facilitate early characterisation of human antibodies allowing researchers to discriminate specific antibodies from non-specific, or 'dirty' antibodies," he added.
The company intends to develop similar arrays for other species commonly used in pharmaceutical research, including mouse, rat and dog.
