Nobel Prizes Recognize Discoveries Central to Biologics Drug Discovery

By Andrew LeBeau | Monday, October 15, 2018 - 17:24 UTC
The Nobel golden medallion with an embossed image of Alfred Nobel

It’s Nobel Prize season and it’s notable that two of the prizes awarded have direct ties to biologics drug discovery.

On October 1st, the 2018 Nobel Prize for Physiology or Medicine was awarded to James P. Allison and Tasuku Honju "for their discovery of cancer therapy by inhibition of negative immune regulation". Allison, currently of MD Anderson Cancer Center at the University of Texas, and Honju, currently of Kyoto University in Japan, are both immunologists and independently discovered key regulatory pathways whereby the body’s immune system can be made more effective in fighting cancer. The novelty of their discoveries was that instead of attacking the cancer cells directly, each researcher discovered a T cell protein that acts as a brake on the immune system. In Allison’s case it was CTLA-4 and in Honju’s PD-1. Antibodies developed against CTLA-4 or to molecules expressed by cancer cells that bind to PD-1, were shown to arrest and in some cases reverse tumor growth. In 2011 the FDA approved Yervoy (ipilimumab) from BMS, an anti-CTLA-4 antibody, to treat melanoma. Then in 2014 the FDA approved Keytruda (pembrolizumab) from Merck, that binds to PD-1 receptors, for use in certain metastatic tumor patients.

Following on from this, on October 3rd the 2018 Nobel Prize in Chemistry was awarded to Frances Arnold, from CalTech, and the other half jointly to George Smith of the University of Missouri and Sir Gregory Winter of Cambridge University. Arnold won the prize for “the directed evolution of enzymes” and Smith and Winter for “the phage display of peptides and antibodies”. In her pioneering work on the directed evolution of enzymes, Arnold opened new concepts in using recombinant biology and mutational analysis to progressively improve the function of proteins in general, and enzymes in particular. This concept is a fundamental element of biologic drug design during the lead optimization phase. Phage display, where bacteria-infecting viruses are used to present the protein product of a gene of interest that has been inserted into the virus. By connecting genotype to phenotype, this technique opens up large scale screening of genes of interest, and variants of them. This works was essential in the development of antibody therapies. It’s notable that this prize that supports biologics drug discovery is in the chemistry category, reflecting the increasing role of chemistry in biologics research.

It's gratifying to see these discoveries being recognized by the Nobel Committee. As makers of informatics software supporting biologics drug discovery (as well as small molecule discovery), we both honor the newly minted laureates and also benefit from their discoveries through the implementation of capabilities in our software that support the application of these techniques.
 

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