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Uğur Şahin

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Uğur Şahin
Ugur Sahin v1.jpg
Şahin in 2019
Born (1965-09-29) 29 September 1965 (age 56)
CitizenshipGermany[1]
Alma mater
OccupationOncologist, immunologist
Years active1991–present
Known for
OfficeCEO BioNTech SE
Term2008–present
Spouse(s)
(m. 2002)
Awards
WebsiteProfile at BioNTech
Signature
Signature of Uğur Şahin.png

Uğur Şahin ([uˈuɾ ʃaː.hin]; born 29 September 1965[citation needed]) is a German oncologist and immunologist. He is the CEO of BioNTech, which helped develop one of the major vaccines against COVID-19.[2][3] His main fields of research are cancer research and immunology.[4]

Şahin's family, originally from Turkey, moved to Germany when he was four years old. He grew up in Cologne and studied medicine at the University of Cologne, completing a doctoral thesis there in cancer immunotherapy. He initially remained in academia, in patient care as an oncohematology physician and conducting research at university hospitals in Saarland and Zürich. He founded a research group at the University of Mainz in 2000 and became a professor of experimental oncology in 2006.

In 2001, while maintaining his position at the University of Mainz, Şahin began to engage in entrepreneurial activities, co-founding two pharmaceutical companies, in 2001 and 2008, with his partner and spouse Özlem Türeci. The second of these companies, BioNTech, together with Pfizer Inc, developed one of the major vaccines used to fight the COVID-19 pandemic in 2020. As a result of the company's increase in value, Şahin and Türeci became the first Germans with Turkish roots among Germany's 100 wealthiest people.[5]

Personal life and education

Şahin was born on 29 September 1965 in İskenderun into a Turkish-Alevi family.[6] He moved with his mother to Germany at the age of four to join his father, who worked in Cologne's Ford factories.[7][8] He was interested in football and popular science books, which he borrowed from the Catholic church library. Initially, his primary school teacher recommended that he attend a hauptschule, which would not have readily enabled him to attend university. Upon intervention of his German neighbour, he went to a gymnasium instead.[9][10][11] Taking advanced courses in mathematic and chemistry, he graduated from the Erich-Kästner-Gymnasium in Cologne-Niehl in 1984, and was the first child at the school with Turkish guest worker parents.[12]

Şahin met his future wife, Özlem Türeci, during his work at the Saarland University Hospital (Universität des Saarlandes) in Homburg, where Türeci completed her last year of medical studies. The couple married in 2002; they have one daughter.[13][14][15]

He and his wife are among the hundred richest people in Germany because of the value of their shareholding in BioNTech.[16] As of May 2021, Bloomberg Billionaires Index estimated his net worth at US$8.35 billion.[2]

Education

Şahin studied medicine at the University of Cologne from 1984 to 1992.[17][18] He received his doctorate in 1992 with a thesis on immunotherapy against tumor cells (bispecific monoclonal antibodies for the activation of cytostatic precursors on tumor cells), which was graded summa cum laude. His thesis supervisor was Michael Pfreundschuh [de]. From 1992 to 1994, he studied mathematics at the Fernuniversität Hagen.[19]

Career

Şahin worked as a physician for internal medicine and hematology/oncology from 1991 to 2000 at the University Hospital of Cologne [de] chaired by Volker Diehl and then at the Saarland University Hospital in Homburg. He habilitated in 1999 in the field of molecular medicine and immunology. After a one-year sabbatical with Hans Hengartner [de] at the Institute for Experimental Immunology of the University Hospital of Zürich in 2000, he joined Christoph Huber at the University Medical Center Mainz. There, he has been working in various leading positions in cancer research and immunology since 2001 and has been a professor for experimental oncology at the Department for Internal Medicine/Oncohematology since 2006.[20] Şahin sees himself as an immune engineer who tries to use the body's antiviral mechanisms to treat, for example, cancer, when the immune system is otherwise unable to fight it. He sees his vision in guiding the immune system is to "protect us from or alleviate certain diseases".[21][22]

University Medical Center Mainz

In 2000, Şahin became head of the junior research group of SFB 432 (Sonderforschungsbereiche, Collaborative Research Centers) of the University Medical Center Mainz [de], and in 2003 chair of the Tumor Vaccine Center.[19][23] Since 2006 he has been a lecturer in the Department of Experimental and Translational Oncology. In 2010, he co-founded TRON (Translational Oncology at the University Medical Center of Johannes Gutenberg University Mainz). TRON is a non-profit (private) biopharmaceutical research institute that develops new diagnostic tools and drugs to treat cancer and other diseases with a high unmet medical need.[24] Its focus is on individualized medicine and cancer immunotherapy. For his work in this field, Şahin was awarded the German Cancer Prize [de].[25][26]

From its foundation until September 2019, he was TRON's scientific director.[27] Since then, he has been working as a scientific advisor and supervisor of Ph.D. students.[28]

Sahin is deputy director of the University Center for Tumor Diseases Mainz (UCT Mainz), founded in 2011.[29][30] The UCT Mainz is an association of all active institutions at the University Medical Center Mainz that focus on clinical oncology or oncological research.[31] In 2017, Sahin was involved in establishing the new Helmholtz Institute HI-TRON, which is a cooperation between the German Cancer Research Center (DKFZ) and TRON.[32][33][34]

He is one of the scientific directors of the new Helmholtz Institute.[35] During the founding ceremony, Şahin declared that he believes "cancer can be defeated in the future".[36] A project that Sahin led at the University Medical Center for developing innovative vaccines against cancer was one of twelve projects awarded a sponsorship prize by the German Federal Ministry of Education and Research in 2006 as part of the newly created biotechnology start-up offensive (GO-Bio).

Ganymed Pharmaceuticals

Şahin co-founded the company Ganymed Pharmaceuticals in 2001 with his wife Özlem Türeci and his mentor Christoph Huber.[37] Ganymed developed the monoclonal antibody Zolbetuximab, for use against esophageal and gastrointestinal cancer.[38] In 2016, after showing in a randomized clinical trial that this drug significantly boosted advanced gastric cancer patients' overall survival,[39] the company was sold to Astellas Pharma for over €400 million.[40] The drug is in Phase III trials as of 2020.[41][42][43]

BioNTech

Headquarters of BioNTech SE in Mainz

Together with Özlem Türeci and Christoph Huber, Şahin founded the biotechnology company BioNTech, based in Mainz, Germany, in 2008 and serves as its CEO.[44][45] BioNTech is focused on developing and manufacturing active immunotherapies for a patient-specific approach to the treatment of cancer and other serious diseases.[46] The main focus of his research work is the discovery of mRNA-based drugs for use as individualized cancer immunotherapies, as vaccines against infectious diseases, and as protein replacement therapies for rare diseases.[47] He holds a minority interest in the listed company.[48][49] Since April 2020, BioNTech has been researching a vaccine for the lung disease COVID-19 under Şahin and Türeci, who is also a member of the company's board of directors.[50][51] Şahin is involved in several patents that he has filed with his company and partners.

Against the background of the debate about the distribution of a potential vaccine, Şahin stated that one key in the fight against COVID-19 is international cooperation and equality of distribution. He said there was "no discussion" about whether a vaccine would be made available exclusively to individual countries.[52][53] Şahin is against compulsory vaccination and emphasizes the voluntary nature of the vaccination.[54]

He also emphasizes that the efficacy and safety of a vaccine, including side effects, must always be communicated transparently. In fall 2020, he entered a partnership with the U.S. pharmaceutical company Pfizer and planned to obtain approval for a vaccine before the end of 2020.[55][56][57] In November, the company reported a 95 percent efficacy of the BNT162b2 vaccine.[58]

Research

Şahin has worked with Türeci as a physician-scientist couple since they met in 1992. Their early work focussed on identifying and characterizing new target molecules (antigens) for the immunotherapy of cancer. They discovered tumor antigens relevant for treatment of various types of cancers, e.g. stomach cancer, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, lung cancer and other dangerous cancers.[59][60][61]

Şahin and his team established strategies that allow different layers of mRNA vaccine optimization, including optimizations of the various structural backbone elements of mRNA molecules, ways to utilize uridine-based as well as nucleoside-modified mRNA chemistries, and different lipid-based compositions and administration routes to deliver mRNA. Systematically combining mRNA modifications achieved an exponential improvement in the potency of mRNA vaccines and its adaption to various purposes.[62][63][64]\\[65][66] Building on this toolbox of improvements of RNA molecules, Şahin successfully used mRNA for applications in humans.

RNA vaccines targeting individual cancer mutations

One application Sahin's team pioneered are mRNA vaccines for personalized cancer therapy that are based on non-nucleoside modified mRNA. This technology relies on targeting tumor-specific mutations that are not present in normal cells. Each patient's tumor has a unique set of mutations. Since mRNA vaccines can be easily designed to target any antigen, the team could use the mutation fingerprint of cancers for engineering mRNA-based personalized neo-antigen vaccines. This application offers the possibility of targeting each patient's tumor mutations with an individually tailored mRNA vaccine of unique composition that is produced "on demand".

RNA vaccines targeting tumor-associated antigens

To apply their RNA cancer vaccine to tumor-associated antigens (TAAs) shared between patients, Sahin and his team developed RNA vaccine nanoparticle delivery strategies that target tissue-derived dendritic cells body-wide. They pioneered the first intravenous nanoparticle delivery of mRNA vaccines in humans. They observed strong tumor-antigen-specific immune responses induced by their uridine-based non-nucleoside modified mRNA vaccines, even though the utilized TAAs are self-antigens. This was a critical step toward the development of effective, potent cancer vaccines targeting a broad range of antigens for immunotherapy.

RNA vaccines to improve CAR-T therapy

Chimeric antigen receptor (CAR)-T cell therapies (CARVAC) are promising immunotherapies for treating B-cell-derived hematologic cancers. Achieving long-term patient responses in solid tumors remains a challenge due to poor activity of CAR-T cells against solid cancer. Sahin and his team have developed ways to use RNA vaccine technology for in vivo expansion and enhanced engraftment of genetically engineered, adoptively transferred CAR-T cells. This has been effective in inducing regression of large tumors in challenging mouse cancer models. The approach is now in clinical trials for the treatment of patients with various cancers.

RNA vaccines to induce antigen-specific tolerance in Autoimmune disease\

Şahin and Türeci during the honorary doctorate ceremony given by the University of Cologne Faculty of Medicine, 2021

Autoimmune diseases, such as multiple sclerosis (MS), result from tissue damage caused by self-reactive T lymphocytes. Combating autoimmune diseases is challenging and can lead to systemic immunosuppression and side effects such as increased risk of infection. Şahin and his team developed a novel therapeutic strategy that circumvents systemic immunosuppression by inhibiting only the immune cells that mediate autoimmune disease. They used a different version of lipid nanoparticles to deliver MS autoantigens encoded by a non-inflammatory RNA into dendritic cells. This approach expands a specific type of immune cells, called antigen-specific regulatory effector T cells, which suppress autoreactivity against the targeted autoantigens and also promote inhibition of autoreactive T cells against other myelin-specific autoantigens. The RNA vaccine used for tolerance induction contained 1-methylpseudouridine (m1Ψ) instead of uridine, a modification previously described by Kariko and colleagues that does not stimulate Toll-like receptors. In mouse models of MS, the novel RNA vaccine approach delayed onset and reduced severity of established disease without inducing generalized immunosuppression.[67][68][69]

RNA vaccine against COVID-19

In January 2020, Sahin and his teams pivoted from cancer to COVID-19 vaccine development. The rapid publication of the sequence of SARS-COV-2 enabled them to initiate an RNA vaccine discovery program. The versatile nature of their mRNA technology and the groundwork Sahin's team had done in the area of cancer vaccines allowed them to develop, produce and test multiple mRNA vaccine candidates in parallel. BNT162b2 was discovered as the best[according to whom?] candidate for the particular purpose of vaccinating for COVID19 prevention. BNT162b2 is a lipid nanoparticle encapsulated, nucleoside-modified RNA vaccine encoding SARS-CoV-2 spike protein and combines multiple features for optimized vaccine activity derived from Sahin, Türeci and their teams prior work.[70][71][62] Clinical trials and subsequent real-world studies established that BNT162b2 vaccine is very effective in inducing immune responses and proved the safety and potent efficacy in humans.[72][73][74] BNT162b2 became the first mRNA drug approved for human use and the fastest vaccine developed against a new pathogen in the history of medicine.[75]

Memberships

Şahin in 2019

Şahin has been a member of the German Society of Immunology [de] since 2004 and a member of the Program Committee of the Association for Cancer Immunotherapy (CIMT), Regulatory Research Group, Mainz, since 2008. In 2012, he was among the founders of the Cluster of Individualized Immunointervention (CI3) in Mainz.[76][77] He has been a member of the American Association for Cancer Research (AACR) since 2014 and of the American Society of Clinical Oncology (ASCO) since 2015.[20] In 2021 Sahin was elected as a member of the European Molecular Biology Organization (EMBO).

Publications

The U.S. National Library of Medicine lists 345 clinical studies and other publications in which Şahin was involved; he is first author of 49.[78] The U.S. Patent and Trademark Office lists several patents related to him.[79]

Based on the top-cited patent over the past five years, and H-index, a calculation of the impact of a researcher's publications over time, Sahin was ranked in Nature Biotechnology's Top 20 translational researchers in the years of 2015,[80] 2018 and 2019.[81]

Selection
  • Sahin, U.; Kariko, K.; Türeci, Ö. (2014), "mRNA-based therapeutics–developing a new class of drugs.", Nature Reviews Drug Discovery, 13 (10), pp. 759–780, doi:10.1093/nar/gku757, PMC 4176373, PMID 25150148
  • Sahin, U.; et al. (2017), "Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer.", Nature, 547 (7662): 222–226, Bibcode:2017Natur.547..222S, doi:10.1038/nature23003, PMID 28678784, S2CID 3757711
  • Polack, Fernando P.; Thomas, Stephen J.; Kitchin, Nicholas; Absalon, Judith; Gurtman, Alejandra; Lockhart, Stephen; Perez, John L.; Pérez Marc, Gonzalo; Moreira, Edson D.; Zerbini, Cristiano; Bailey, Ruth; Swanson, Kena A.; Roychoudhury, Satrajit; Koury, Kenneth; Li, Ping; Kalina, Warren V.; Cooper, David; Frenck, Robert W.; Hammitt, Laura L.; Türeci, Özlem; Nell, Haylene; Schaefer, Axel; Ünal, Serhat; Tresnan, Dina B.; Mather, Susan; Dormitzer, Philip R.; Şahin, Uğur; Jansen, Kathrin U.; Gruber, William C. (2020), "Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine", New England Journal of Medicine, 383 (27): 2603–15, doi:10.1056/NEJMoa2034577, hdl:10757/655958, PMC 7745181, PMID 33301246, S2CID 228087117
  • Miller, Joe; Şahin, Uğur; Türeci, Özlem (2021). Projekt Lightspeed: Der Weg zum BioNTech-Impfstoff [Project Lightspeed: The Road to the BioNTech Vaccine] (in German) (1st ed.). Hamburg: Rowohlt Verlag. p. 352. ISBN 978-3-498-00277-0.

Awards (selection)

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