Gregory Winter

Sir Gregory Paul Winter CBE FRS FMedSci (born 14 April 1951)[6][7] is a Nobel Prize-winning British molecular biologist best known for his work on the therapeutic use of monoclonal antibodies. His research career has been based almost entirely at the MRC Laboratory of Molecular Biology and the MRC Centre for Protein Engineering, in Cambridge, England.

For the American journalist, see Greg Winter (journalist).
Sir Gregory Winter

CBE FRS FMedSci
'
Born
Gregory Paul Winter

(1951-04-14) 14 April 1951
Leicester, Leicestershire, England
CitizenshipUnited Kingdom
EducationRoyal Grammar School, Newcastle upon Tyne
Alma materTrinity College, Cambridge (MA, PhD)
Known forCambridge Antibody Technology
Domantis[1]
Bicycle Therapeutics[2]
Antibody engineering
AwardsColworth Medal (1986)
EMBO Member (1987)[3]
Louis-Jeantet Prize for Medicine (1989)[4]
Knight Bachelor (2004)
Royal Medal (2011)
Prince Mahidol Award (2016)[5]
Nobel Prize in Chemistry (2018)
Scientific career
FieldsBiochemistry
InstitutionsUniversity of Cambridge
Laboratory of Molecular Biology
Imperial College London
ThesisThe amino acid sequence of tryptophanyl tRNA synthetase from Bacillus stearothermophilus (1977)
Doctoral advisorBrian S. Hartley
WebsiteLMB web page

He is credited with invented techniques to both humanise (1986) and, later, to fully humanise using phage display, antibodies for therapeutic uses.[2][8][9][10][11][12][13] Previously, antibodies had been derived from mice, which made them difficult to use in human therapeutics because the human immune system had anti-mouse reactions to them.[6][14][15][16][17][18] For these developments Winter was awarded the 2018 Nobel Prize in Chemistry along with George Smith and Frances Arnold.[19][20]

He is a Fellow of Trinity College, Cambridge and was appointed Master of Trinity College, Cambridge on 2 October 2012.[21] From 2006 to 2011, he was Deputy Director of the Laboratory of Molecular Biology, Medical Research Council, acting Director from 2007 to 2008 and Head of the Division of Protein and Nucleic Acids Chemistry from 1994 to 2006. He was also Deputy Director of the MRC Centre for Protein Engineering from 1990 to its closure in 2010.[22][23]

Education

Winter was educated at the Royal Grammar School, Newcastle upon Tyne.[6] He went on to study Natural Sciences at the University of Cambridge graduating from Trinity College, Cambridge in 1973. He was awarded a PhD degree, from the MRC Laboratory of Molecular Biology, for research on the amino acid sequence of tryptophanyl tRNA synthetase from the bacterium Bacillus stearothermophilus in 1977[24] supervised by Brian S. Hartley.[25] Later, Winter completed a term of post-doctoral fellowship at Imperial College London, and another at the Institute of genetics in University of Cambridge.[26]

Career and research

Following his PhD, Winter completed postdoctoral research at the Laboratory of Molecular Biology in Cambridge.[27][28] He continued to specialise in protein and nucleic acid sequencing and became a Group Leader at the MRC Laboratory of Molecular Biology in 1981. He became interested in the idea that all antibodies have the same basic structure, with only small changes making them specific for one target. Georges Köhler and César Milstein had won the 1984 Nobel Prize for their work at the Laboratory of Molecular Biology, in discovering a method to isolate and reproduce individual, or monoclonal, antibodies from among the multitude of different antibody proteins that the immune system makes to seek and destroy foreign invaders attacking the body.[29] However, these monoclonal antibodies had limited application in human medicine, because mouse monoclonal antibodies are rapidly inactivated by the human immune response, which prevents them from providing long-term benefits.

Winter then pioneered a technique to "humanise" mouse monoclonal antibodies; a technique that was used in the development of Campath-1H  by the Laboratory of Molecular Biology and University of Cambridge scientists.[30] This antibody now looks promising for the treatment of multiple sclerosis. Humanised monoclonal antibodies form the majority of antibody-based drugs on the market today and include several blockbuster antibodies, such as Keytruda, which works with your immune system to help fight certain cancers.

Winter founded Cambridge Antibody Technology in 1989,[31][32] and Bicycle Therapeutics.[33][34] He worked on the Scientific Advisory Board of Covagen,[35][36] (now part of Cilag) and is also the chairman of the Scientific Advisory Board for Biosceptre International Limited.

In 1989, Winter was a founder of Cambridge Antibody Technology, one of the early commercial biotech companies involved in antibody engineering. One of the most successful antibody drugs developed was HUMIRA (adalimumab), which was discovered by Cambridge Antibody Technology as D2E7, and developed and marketed by Abbott Laboratories. HUMIRA, an antibody to TNF alpha, was the world's first fully human antibody,[37] which went on to become the world's top selling pharmaceutical with sales of over $18Bn in 2017[38] Cambridge Antibody Technology was acquired by AstraZeneca in 2006 for £702m.[39]

In 2000, Winter founded Domantis to pioneer the use of domain antibodies, which use only the active portion of a full-sized antibody. Domantis was acquired by the pharmaceutical GlaxoSmithKline in December 2006 for £230 million.[1][40]

Winter subsequently founded another company, Bicycle Therapeutics Limited as a start up company which is developing very small protein mimics based on a covalently bonded hydrophobic core.[41]

Awards and honours
Greg Winter during Nobel press conference in Stockholm, December 2018

Winter was elected a Fellow of the Royal Society (FRS) in 1990[42] and awarded the Royal Medal by the society in 2011 "for his pioneering work in protein engineering and therapeutic monoclonal antibodies, and his contributions as an inventor and entrepreneur".[43] He was given the Scheele Award in 1994.

In 1995, Winter won several international awards including the King Faisal International Prize for Medicine (Molecular Immunology) and in 1999, the Cancer Research Institute William B. Coley Award. Winter was formerly the Joint Head of the Division of Protein and Nucleic acid Chemistry-Biotechnology, and is Deputy Director,[44] at the Laboratory of Molecular Biology, Cambridge, an institution funded by the UK Medical Research Council. He was also Deputy Director of the MRC's Centre for Protein Engineering until its absorption into the Laboratory of Molecular Biology. He is a member of the Advisory Council for the Campaign for Science and Engineering.[45] Winter was appointed Commander of the Order of the British Empire (CBE) in 1997 and Knight Bachelor in 2004. He served as Master of Trinity College, Cambridge from 2012 to 2019.[46][47] In 2015 he received the Wilhelm Exner Medal.[48]

Winter was awarded the Nobel Prize in Chemistry on 3 October 2018 for his work on phage displays for antibodies, along with George Smith and Frances Arnold.[19] In 2020 he was featured on The Times' 'Science Power List'.[49]

References
  1. "GSK snaps up Domantis to move into biotech field". The Independent. 9 December 2006.
  2. The Scientific Founders Archived 13 September 2011 at the Wayback Machine of Bicycle Therapeutics Ltd. – Christian Heinis and Sir Greg Winter, FRS.
  3. "EMBO MEMBER: Gregory P. Winter". people.embo.org.
  4. "Doctor Gregory P. WINTER | Jeantet". 1 October 2017.
  5. "Announcement of the Prince Mahidol Award 2016". princemahidolaward.org. Archived from the original on 14 November 2017. Retrieved 13 June 2017.
  6. "WINTER, Sir Gregory (Paul)". Who's Who. ukwhoswho.com. 2016 (online Oxford University Press ed.). A & C Black, an imprint of Bloomsbury Publishing plc. (subscription or UK public library membership required) (subscription required)
  7. "Sir Gregory P. Winter – Facts – 2018". NobelPrize.org. Nobel Media AB. 6 October 2018. Retrieved 6 October 2018.
  8. McCafferty, J.; Griffiths, A.; Winter, G.; Chiswell, D. (1990). "Phage antibodies: filamentous phage displaying antibody variable domains". Nature. 348 (6301): 552–554. Bibcode:1990Natur.348..552M. doi:10.1038/348552a0. PMID 2247164. S2CID 4258014.
  9. "Trinity College Cambridge". Archived from the original on 6 March 2012.
  10. Gregory Winter's publications indexed by the Scopus bibliographic database. (subscription required)
  11. Winter, G; Griffiths, A. D.; Hawkins, R. E.; Hoogenboom, H. R. (1994). "Making antibodies by phage display technology". Annual Review of Immunology. 12: 433–455. doi:10.1146/annurev.iy.12.040194.002245. PMID 8011287.
  12. Griffiths, A. D.; Williams, S. C.; Hartley, O; Tomlinson, I. M.; Waterhouse, P; Crosby, W. L.; Kontermann, R. E.; Jones, P. T.; Low, N. M.; Allison, T. J. (1994). "Isolation of high affinity human antibodies directly from large synthetic repertoires". The EMBO Journal. 13 (14): 3245–60. doi:10.1002/j.1460-2075.1994.tb06626.x. PMC 395221. PMID 8045255.
  13. Hoogenboom, H. R.; Griffiths, A. D.; Johnson, K. S.; Chiswell, D. J.; Hudson, P.; Winter, G. (1991). "Multi-subunit proteins on the surface of filamentous phage: Methodologies for displaying antibody (Fab) heavy and light chains". Nucleic Acids Research. 19 (15): 4133–4137. doi:10.1093/nar/19.15.4133. PMC 328552. PMID 1908075.
  14. Anon (2011). "The inventor of humanized monoclonal antibodies and cofounder of Cambridge Antibody Technology, Greg Winter, muses on the future of antibody therapeutics and UK life science innovation". Nature Biotechnology. 29 (3): 190. doi:10.1038/nbt.1815. PMID 21390009. S2CID 205275386.
  15. Winter, G.; Fields, S.; Brownlee, G. G. (1981). "Nucleotide sequence of the haemagglutinin gene of a human influenza virus H1 subtype". Nature. 292 (5818): 72–5. Bibcode:1981Natur.292...72W. doi:10.1038/292072a0. PMID 7278968. S2CID 4312205.
  16. Fields, S.; Winter, G.; Brownlee, G. G. (1981). "Structure of the neuraminidase gene in human influenza virus A/PR/8/34". Nature. 290 (5803): 213–7. Bibcode:1981Natur.290..213F. doi:10.1038/290213a0. PMID 7010182. S2CID 8051512.
  17. Riechmann, L.; Clark, M.; Waldmann, H.; Winter, G. (1988). "Reshaping human antibodies for therapy". Nature. 332 (6162): 323–7. Bibcode:1988Natur.332..323R. doi:10.1038/332323a0. PMID 3127726. S2CID 4335569.
  18. Marks, J. D.; Hoogenboom, H. R.; Bonnert, T. P.; McCafferty, J.; Griffiths, A. D.; Winter, G. (1991). "By-passing immunization". Journal of Molecular Biology. 222 (3): 581–97. doi:10.1016/0022-2836(91)90498-U. PMID 1748994.
  19. "Live blog: direction evolution takes chemistry Nobel prize". Retrieved 3 October 2018.
  20. "Nobel Prize in Chemistry 2018 – live". The Guardian. 3 October 2018. Retrieved 3 October 2018.
  21. http://www.takedasf.com/corporate/winter.htm. Missing or empty |title= (help)
  22. "Sir Gregory Winter Chairman". Archived from the original on 29 January 2012.
  23. "Greg Winter wins 2018 Nobel Prize for Chemistry - MRC Laboratory of Molecular Biology". MRC Laboratory of Molecular Biology. 3 October 2018. Retrieved 7 October 2018.
  24. Winter, Gregory Paul (1976). The amino acid sequence of tryptophanyl RNA synthetase from bacillus stearothermophilus (PhD thesis). University of Cambridge. OCLC 500591023. EThOS uk.bl.ethos.477727.
  25. Winter, G. P.; Hartley, B. S. (1977). "The amino acid sequence of tryptophanyl tRNA Synthetase fromBacillus stearothermophilus". FEBS Letters. 80 (2): 340–342. doi:10.1016/0014-5793(77)80471-7. ISSN 0014-5793. PMID 891985. S2CID 39202845.
  26. "King Faisal Prize | Professor Sir Gregory P. Winter". kingfaisalprize.org. Retrieved 4 October 2018.
  27. "Scientific Advisory Board". Heptares. Retrieved 5 April 2013.
  28. Gregory Winter publications indexed by Google Scholar
  29. "The Nobel Prize in Physiology or Medicine 1984". NobelPrize.org. Retrieved 7 October 2018.
  30. "Therapeutic Antibodies - MRC Laboratory of Molecular Biology". MRC Laboratory of Molecular Biology. Retrieved 7 October 2018.
  31. "Greg Winter". MRC Laboratory of Molecular Biology.
  32. "Sir Gregory Winter | Royal Society".
  33. Gregory Winter (8 May 2001). "Gregory Winter: Executive Profile & Biography – Businessweek". Bloomberg BusinessWeek. Retrieved 5 April 2013.
  34. "www.bicycletherapeutics.com". bicycletherapeutics.com. 10 December 2012. Retrieved 5 April 2013.
  35. "Covagen AG | September 2011: Sir Gregory Winter joins Covagen's Scientific Advisory Board". Covagen.com. 20 September 2011. Archived from the original on 26 April 2012. Retrieved 5 April 2013.
  36. "Covagen AG | Scientific Advisory Board". Covagen.com. Archived from the original on 26 April 2012. Retrieved 5 April 2013.
  37. Lawrence, Stacy (2007). "Billion dollar babies—biotech drugs as blockbusters". Nature Biotechnology. 25 (4): 380–2. doi:10.1038/nbt0407-380. PMID 17420735. S2CID 205266758.
  38. "Global Pharmaceutical 2017 Industry Statistics" (PDF). Retrieved 3 October 2018.
  39. http://www.astrazeneca.com/media/latest-press-releases/2006/5266?itemId=3891617 Archived 2 January 2010 at the Wayback Machine
  40. GSK is to buy Domantis – a company based on discoveries by MRC scientists Archived 16 January 2014 at the Wayback Machine LMB webpage
  41. Heinis, C.; Rutherford, T.; Freund, S.; Winter, G. (2009). "Phage-encoded combinatorial chemical libraries based on bicyclic peptides". Nature Chemical Biology. 5 (7): 502–507. doi:10.1038/nchembio.184. PMID 19483697.
  42. "Sir Gregory Winter CBE FMedSci FRS". London: Royal Society. Archived from the original on 17 November 2015.
  43. "Royal Society announces 2011 Copley Medal recipient". Royal Society. Retrieved 23 February 2012.
  44. "LMB Structure". Archived from the original on 23 February 2008.
  45. "Advisory Council of the Campaign for Science and Engineering". Archived from the original on 28 August 2010. Retrieved 11 February 2011.
  46. "Sir Gregory Winter CBE FRS appointed Master of Trinity College, Cambridge University". 10 Downing Street. 16 December 2011. Retrieved 5 April 2013.
  47. "Master of Trinity College, Cambridge &' events". University of Cambridge. Archived from the original on 12 July 2012. Retrieved 5 April 2013.
  48. Sir Gregory Winter, retrieved on 17 March 2020 in Wilhelmexner.org
  49. Franklin-Wallis, Oliver (23 May 2020). "From pandemics to cancer: the science power list". The Times. ISSN 0140-0460. Retrieved 26 May 2020.

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