John McCafferty

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John McCafferty is a British scientist, one of the founders of Cambridge Antibody Technology alongside Sir Gregory Winter and David Chiswell. He is well known as one of the inventors of scFv antibody fragment phage display, [1] a technology that revolutionised the monoclonal antibody drug discovery. McCafferty and his team developed this process following failures previously generating antibodies by immunizing mice. [2] Later improvements of antibody phage display technology enables the display of millions of different antibody fragments on the surface of filamentous phage (better known as antibody phage library) and subsequent selection of highly specific recombinant antibodies to any given target. This technology is widely exploited in pharmaceutical industry for the discovery and development of therapeutic monoclonal antibodies to treat mainly cancer, inflammatory and infectious diseases. One of the most successful was HUMIRA (adalimumab), 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 phage display derived fully human antibody, [3] which achieved annual sales exceeding $1bn [4] therefore achieving blockbuster status. Humira went on to dominate the best-selling drugs lists - in 2016: The best selling drugs list researched by Genetic Engineering & Biotechnology News, published in March 2017, details that Humira occupied the number 1 position for 2015 ($14.012 billion) and 2016 ($16.078 billion). [5] Whilst for 2017, Abbvie reports that Humira achieved $18.427billion of sales in 2017 [6]

In 2002, after 12 years in Cambridge Antibody Technology (now MedImmune, a fully owned subsidiary of pharmaceutical giant AstraZeneca), McCafferty set up a group at the Sanger Institute developing and utilising methods for protein generation and recombinant antibody isolation in high throughput for proteomic applications. McCafferty has been involved in developing large human antibody repertoires both at CAT and at the Sanger Institute from which antibodies of high affinity and specificity to any antigen can be derived. He ran a laboratory at the Biochemistry Dept at University of Cambridge capitalising on the above technologies with a focus on the study of protein:protein interactions driving direct cell:cell communication [7] [8] [9] [10] [11] [12] and has recently founded a new therapeutic antibody discovery biotechnology company, IONTAS Ltd.

In 2018, McCafferty's 1990 phage research paper was cited by the Nobel committee when awarding the chemistry prize to Sir Gregory Winter and George Smith. [13]

Related Research Articles

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James Allen Wells is a Professor of Pharmaceutical Chemistry and Cellular & Molecular Pharmacology at the University of California, San Francisco (UCSF) and a member of the National Academy of Sciences. He received his B.A. degrees in biochemistry and psychology from University of California, Berkeley in 1973 and a PhD in biochemistry from Washington State University with Ralph Yount, PhD in 1979. He completed his postdoctoral studies at Stanford University School of Medicine with George Stark in 1982. He is a pioneer in protein engineering, phage display, fragment-based lead discovery, cellular apoptosis, and the cell surface proteome.

References

  1. ↑ McCafferty J; Griffiths A.D; Winter G; Chiswell D.J (1990). "Phage antibodies: filamentous phage displaying antibody variable domains". Nature. 348 (63017): 552–554. Bibcode:1990Natur.348..552M. doi:10.1038/348552a0. PMID   2247164. S2CID   4258014.
  2. ↑ "Dr John McCafferty on how his antibody phage display work contributed to a Nobel Prize". Next Generation Therapeutics.
  3. ↑ Lawrence, Stacy (2007). "Billion dollar babies—biotech drugs as blockbusters". Nature Biotechnology. 25 (4): 380–382. doi:10.1038/nbt0407-380. PMID   17420735. S2CID   205266758.
  4. ↑ "Cambridge Antibody: Sales update | Company Announcements | Telegraph". Archived from the original on 2011-07-17. Retrieved 2009-07-27.
  5. ↑ "The Top 15 Best-Selling Drugs of 2016". 6 March 2017.
  6. ↑ "AbbVie Reports Full-Year and Fourth-Quarter 2017 Financial Results | AbbVie News Center".
  7. ↑ "Research in the Department of Biochemistry". Archived from the original on 2009-12-08. Retrieved 2009-12-23.
  8. ↑ http://www.repairingthebody.com/jmccafferty.html%5B%5D
  9. ↑ Schofield DJ, Pope A, Clementel V, Buckell J, Chapple SDJ,, Clarke KF, Conquer JS, Crofts AM, Crowther SRE, Dyson MR, Flack G, Griffin GJ, Hooks Y, Howat WJ, Kolb-Kokocinski A,, Kunze S, Martin CD, Maslen GL,, Mitchell JM, OÕSullivan M, Perera RL, Roake W, Shadbolt SP, Vincent KJ, Warford A, Wilson WE, Xie J, Young JL, McCafferty J (2007) Application of phage display to high throughput antibody generation and characterisation. Genome Biology. 8 (11) R254
  10. ↑ Dyson MR, Perera RL, Shadbolt SP, Biderman L, Bromek K, Murzina NV, McCafferty J (2008) Identification of soluble protein fragments by gene fragmentation and genetic selection. Nucl Acid Research 36 e51 http://nar.oxfordjournals.org/cgi/reprint/36/9/e51
  11. ↑ Teng MS, Shadbolt P, Fraser AG, Jansen G, and McCafferty J. (2008) Control of feeding behaviour in C. elegans by human G protein coupled receptors permits screening for agonist-expressing bacteria. Proc Natl Acad Sci, 105 (39) 14826-14831
  12. ↑ Chapple SDJ, Crofts AM, Shadbolt SP, McCafferty J, Dyson MR (2006) Multiplexed expression and screening for recombinant protein production in mammalian cells. BMC Biotechnology 6:49 http://www.biomedcentral.com/1472-6750/6/49
  13. ↑ "Dr John McCafferty on how his antibody phage display work contributed to a Nobel Prize". Next Generation Therapeutics.
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