An article from the May issue of Nature entitled: Reproducibility Crisis: Blame it on the Antibodies was shared and circulated widely in biotechnology forums and social media platforms. The widespread interest in the article speaks to the commonly shared industry frustration over antibodies not performing well in end use assays. The explosion of genomic and proteomic medicine over the last few decades has indeed created an insurmountable challenge for the antibody retail sales model. The rapid growth of the number of antibody targets of interest, combined with increasingly nuanced desired epitopes, makes having a comprehensive, well-supported catalog nearly impossible. As a result, antibody retailers are forced to scoop up large numbers of existing antibodies for resale without devoting adequate resources to validation.
It is often suggested, as it is in the Nature article, that increased transparency in reporting, data sharing, and honest reviews of retail antibodies is the solution to the dilemma. It certainly can’t hurt and at MBS we have participated in a number of programs to help increase the data sharing and reviews of our small catalog of retail antibodies. We believe, however, that there is a larger indication that most early drug discovery research that requires reproducibility and certainty, will require custom designed monoclonal antibodies.
The Nature article does not differentiate between the functionality of monoclonal and polyclonal antibodies. Many of the specificity failures addressed would be improved by using a well proven monoclonal antibody. As it stands, many more polyclonals exist in the retail antibody market. Researchers are often reluctant to devote time and substantial money to the development of reagents for their work; however, countless research variables means that there will likely never be a one size fits all validation system for catalogs.
Even for custom antibody developers, the challenge to meet researchers’ needs is real. Projects are growing in difficulty and assay goals can change mid project with both successes and setbacks of simultaneous drug development or research. The only way to ensure a functional antibody is to partner with antibody companies that can accumulate adequate screening data and communicate efficiently enough that antibody candidate selection can change readily in response to evolving parameters. One strategy used by MBS is to develop a rich data package from libraries of purified and biotinylated antibody candidates to allow for extensive early screenings. These early sample plates can be used to assess matched pair compatibility, sensitivity, and specificity against cross-reactants of concern before the customer invests in subcloning and production of untested antibodies. Looking at multiple factors including antibody characteristics, assay coating conditions, and assay format takes the guesswork out of narrowing down an overwhelming number of fusion positives. Perhaps more importantly, it gives the MBS technical team and customers characterized antibody candidates to go back to if project goals change rather than having to start the hybridoma development process over. Whatever the strategy or tools used by antibody companies, researchers must be asking their antibody partners how they are making educated clone selection decisions. If end use functionality is not being considered at clones selection, then the customer may find themselves with the same frustrations created by buying ready to use catalog antibody reagents.
Reproducibility Crisis: Blame it on the Antibodies serves as a constructive starting point for consideration of how we regard the importance of the “workhorses” of scientific research, our antibodies. The article correctly assesses the critical role that antibodies play in drug discovery. That role is indeed too critical to risk a plug-in option off the retail shelf. Antibody project planning, thoughtful antigen design, and thorough screening represent the only true solution. Just as the end uses for antibodies have changed and become more complex, so should the process for developing and characterizing them.
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