Professor Dario Neri, Department of Chemistry and Applied Biosciences, ETH Zürich

From encoded combinatorial libraries to targeted therapeutics

Human antibodies can be isolated against virtually every protein targets by panning suitable binding specificities from phage display libraries. In full analogy, it is becoming increasingly easier to isolate small organic ligands to protein targets of interest using DNA-encoded chemical libraries. 

In this lecture, I will show how we have used encoded combinatorial libraries to discover antibodies and small organic ligands, which have been modified in order to generate pharmaceutical agents, which are currently being investigated in clinical trials.

References:

• DNA-Encoded Chemical Libraries: A Selection System Based on Endowing Organic Compounds with Amplifiable Information. Neri D, Lerner RA. Annu Rev Biochem. 2018 Jun 20;87:479-502.

• Versatile protein recognition by the encoded display of multiple chemical elements on a constant macrocyclic scaffold. Li Y, De Luca R, Cazzamalli S, Pretto F, Bajic D, Scheuermann J, Neri D. Nat Chem. 2018 Apr;10(4):441-448.

• Chemically Defined Antibody- and Small Molecule-Drug Conjugates for in Vivo Tumor Targeting Applications: A Comparative Analysis. Cazzamalli S, Dal Corso A, Widmayer F, Neri D. J Am Chem Soc. 2018 Feb 7;140(5):1617-1621.

• Sarcoma Eradication by Doxorubicin and Targeted TNF Relies upon CD8+ T-cell Recognition of a Retroviral Antigen. Probst P, Kopp J, Oxenius A, Colombo MP, Ritz D, Fugmann T, Neri D. Cancer Res. 2017 Jul 1;77(13):3644-3654.

• Enhanced Therapeutic Activity of Non-Internalizing Small-Molecule-Drug Conjugates Targeting Carbonic Anhydrase IX in Combination with Targeted Interleukin-2. Cazzamalli S, Ziffels B, Widmayer F, Murer P, Pellegrini G, Pretto F, Wulhfard S, Neri D. Clin Cancer Res. 2018, 24: 3656-3667

Short bio

Dario Neri was born in Rome on 1 May 1963, but grew up in Siena (Italy). He studied Chemistry at the Scuola Normale Superiore of Pisa and earned a PhD in Chemistry at the Swiss Federal Institute of Technology (ETH Zürich), under the supervision of Professor Kurt Wüthrich (Nobel Prize Chemistry 2002). After a post-doctoral research internship (1992-1996) at the Medical Research Council Centre in Cambridge (UK), under the supervision of Sir Gregory Winter (Nobel Prize Chemistry 2018), he became professor at ETH Zürich in 1996. Dario Neri is currently Full Professor of Biomacromolecules at the Department of Chemistry and Applied Biosciences, ETH Zürich. The research of the Neri group focuses on the engineering of therapeutic antibodies for the therapy of cancer and other angiogenesis-related disorders and on the development of DNA-encoded chemical libraries. Dario Neri is a co-founder of Philogen (www.philogen.com), a Swiss-Italian biotech company which has brought various antibody products into multicenter clinical trials for the treatment of cancer and of chronic inflammatory conditions. Dario Neri has published over 350 articles in peer-reviewed scientific journals. He is the recipient of the ISOBM Abbott Prize 2000, of the Amgen-Dompe’ Biotec Award 2000, of the Mangia d’Oro 2001, of the Prous Award 2006 of the European Federation of Medicinal Chemistry, of the Robert-Wenner-Prize 2007 of the Swiss Cancer League, of the SWISS BRIDGE Award 2008, of the Prix Mentzer of the French Medicinal Chemistry Society in 2011, of the Phoenix Prize 2014 and of an ERC Advanced Grant in 2015. 

Host: Associate Professor Alex Zelikin, iNANO & Department of Chemistry, AU