E. Sally Ward

For the aristocrat, see Sallie Ward.
Sally Ward
FRS
Born
Elizabeth Sally Ward
Alma materUniversity of Cambridge
AwardsRoyal Society Wolfson Research Merit Award (2018)
Scientific career
FieldsImmunology
Cancer Biology
Antibody Engineering
Antibody Therapeutics[1]
InstitutionsTexas A&M University
University of Texas Southwestern Medical Center
University of Cambridge
University of Southampton
ThesisMolecular genetics of an insectidal delta-endotoxin from Bacillus thuringiensis var israelensis. (1985)
Doctoral advisorDavid J. Ellar
Websitewww.wardoberlab.com/lab-members/sally-ward/

Elizabeth Sally Ward FRS is currently the Director of Translational Immunology at the Centre for Cancer Immunology in the University of Southampton.[1][2] She was elected Fellow of the Royal Society in 2022 in recognition of her research related to the receptor, FcRn, and the development of antibody therapeutics.[3]

Early life and education

Ward was an undergraduate student at the University of Cambridge, where she studied the Natural Sciences Tripos with a focus on biochemistry. She remained at Cambridge for her doctoral research, working under the supervision of David J. Ellar at Gonville and Caius College, Cambridge.[4][5][6] Her PhD research investigated the genetics of delta endotoxin from Bacillus thuringiensis israelensis.[7]

Research and career

Ward remained at Cambridge as a Junior Research Fellow at Gonville and Caius College and subsequently as the Stanley Elmore Senior Research fellow at Sidney Sussex College, Cambridge.[8] During this time, she carried out research in the Department of Biochemistry, and subsequently worked with the 2018 Nobel Laureate, Sir Gregory Winter, on antibody repertoire technology at the MRC Laboratory of Molecular Biology in Cambridge.[9]

In 1990, Ward moved to the United States. She joined the University of Texas Southwestern Medical Center, where she was a member of the founding faculty of the Centre for Immunology. In 2004, she was awarded the Paul and Betty Meek-FINA Professorship.[10] She moved to the Texas A&M University Health Sciences University in 2014.[10] In 2018, Ward returned to the United Kingdom, joining the University of Southampton as Professor of Molecular Immunology and Director of Translational Immunology.[11][12]

Ward's primary research interests have been directed towards understanding the factors that regulate the persistence and transport of antibodies in the body. This has relevance to the maintenance of immunity, in addition to the successful delivery of therapeutic antibodies. In 1996, Ward's laboratory addressed a longstanding question in immunology by identifying the neonatal Fc receptor, FcRn, as the regulator of Immunoglobulin G (IgG) levels and transport in the body.[13] The identification of FcRn as a critical player in these processes also confirmed the 30-year old Brambell hypothesis (F.W.R. Brambell)[14] that connected IgG transport and persistence.

Ward's research has involved the use of molecular and cellular approaches to establish the mechanism by which Fcrn achieves the regulation of antibody persistence and levels. To investigate the cellular processes involving FcRn, in collaboration with Raimund Ober, Ward developed advanced microscopy techniques to track FcRn and IgG in live cells.[15][16][17][18] Ward's molecular and cellular studies have been used to inform the development of new approaches for antibody drug development.

The knowledge of the central role of FcRn in regulating antibody levels was used to develop an approach to extend the in vivo persistence of antibodies, namely half-life extension (HLE).[19] This approach leads to substantial increases in the longevity of antibody-based drugs, allowing lower dosing frequencies. HLE has been widely implemented by biopharma and is used in several clinically approved antibody therapeutics (e.g.[20][21]), with many more in ongoing clinical trials.

Ward's identification of the role of FcRn in regulating IgG levels has led to the development of FcRn antagonists (or inhibitors) that lower antibody levels. Specifically, Ward developed an engineered antibody, called an Abdeg (for antibody that enhances IgG degradation), to inhibit FcRn.[22] The Abdeg technology was licensed to the biopharma company, argenx, and led to the first approved FcRn antagonist, efgartigimod.[23][24][25] Efgartigimod is approved to treat several autoantibody-mediated diseases, and its approval has been followed by that of additional FcRn antagonists developed by other companies.

To address the need for treatments for autoimmune disease that are not immunosuppressive, Ward's laboratory pioneered an approach for the specific removal of antibodies that cause disease in autoimmunity or other antibody-mediated pathologies.[26] This has been named Seldeg technology (for selective degradation).

Ward's research has also involved the use of cell biological studies to generate engineered antibody-drug conjugates (ADCs) that are more effective in delivering cytotoxic drugs to tumor cells for the treatment of cancer.[27] This approach, called ALTA technology, is expected to lead to reduced side-effects due to undesirable toxicities that can currently limit the effective use of ADCs to treat cancer.

Awards and honours

Selected publications

  • Binding activities of a repertoire of single immunoglobulin variable domains secreted from Escherichia coli[9]
  • Abnormally short serum half-lives of IgG in beta 2-microglobulin-deficient mice[13]
  • Increasing the serum persistence of an IgG fragment by random mutagenesis[19]
  • Engineering the Fc region of immunoglobulin G to modulate in vivo antibody levels[22]
  • Engineered clearing agents for the selective depletion of antigen-specific antibodies[26]
  • Engineering a HER2-specific antibody-drug conjugate to increase lysosomal delivery and therapeutic efficacy[27]

References

  1. ^ a b E. Sally Ward publications indexed by Google Scholar
  2. ^ E. Sally Ward publications from Europe PubMed Central
  3. ^ a b "Sally Ward FRS". The Royal Society. London: Royal Society. 2022. Archived from the original on 2023-12-08. Retrieved 2025-10-02.
  4. ^ Anon (2020). "Professor David Ellar (1939 - 2020)". cai.cam.ac.uk.
  5. ^ Susana Vilchez (3 December 2020). "A Tribute to a <i>Bacillus thuringiensis</i> Master: Professor David J. Ellar". Toxins. 12 (12). doi:10.3390/TOXINS12120764. ISSN 2072-6651. PMID 33287128. Wikidata Q104108938.
  6. ^ Anon (2018). "Cancer Institute Seminar Series - Prof Sally Ward". ucl.ac.uk. UCL Cancer Institute. Retrieved 2022-05-11.
  7. ^ Ward, Elizabeth Sally (1985). Molecular genetics of an insectidal delta-endotoxin from Bacillus thuringiensis var israelensis. cam.ac.uk (PhD thesis). University of Cambridge. OCLC 499855244. EThOS uk.bl.ethos.377842.
  8. ^ Anon. "Home". wardoberlab.com. WardOber Lab. Retrieved 2022-05-11.
  9. ^ a b Ward ES; Güssow D; Griffiths AD; Jones PT; Winter G (1 October 1989). "Binding activities of a repertoire of single immunoglobulin variable domains secreted from Escherichia coli". Nature. 341 (6242): 544–546. doi:10.1038/341544A0. ISSN 1476-4687. PMID 2677748. Wikidata Q35896400.
  10. ^ a b Shive, Holly (2014-09-24). "Husband and wife research duo join Texas A&M, advance novel protein engineering research to combat cancer". Vital Record. Texas A&M Health. Archived from the original on 2025-03-31. Retrieved 2025-10-22.
  11. ^ Anon (2019). "Lab Members". wardoberlab.com. WardOber Lab. Retrieved 2022-05-11.
  12. ^ "Interview with Sally Ward and Raimund Ober". southampton.ac.uk. Centre for Cancer Immunology. Retrieved 2022-05-11.
  13. ^ a b Ghetie, Victor; Hubbard, James G.; Kim, Jin-Kyoo; Tsen, May-Fang; Lee, Yukfung; Ward, E. Sally (1996). "Abnormally short serum half-lives of IgG in β2-microglobulin-deficient mice". European Journal of Immunology. 26 (3): 690–696. doi:10.1002/eji.1830260327. ISSN 1521-4141.
  14. ^ Brambell, F. W. R.; Hemmings, W. A.; Morris, I. G. (1964-09-24). "A Theoretical Model of γ-Globulin Catabolism". Nature. 203 (4952): 1352–1355. doi:10.1038/2031352a0. ISSN 1476-4687.
  15. ^ Prabhat, Prashant; Gan, Zhuo; Chao, Jerry; Ram, Sripad; Vaccaro, Carlos; Gibbons, Steven; Ober, Raimund J.; Ward, E. Sally (2007-04-03). "Elucidation of intracellular recycling pathways leading to exocytosis of the Fc receptor, FcRn, by using multifocal plane microscopy". Proceedings of the National Academy of Sciences. 104 (14): 5889–5894. doi:10.1073/pnas.0700337104. PMC 1851587. PMID 17384151.
  16. ^ Ober, Raimund J.; Martinez, Cruz; Vaccaro, Carlos; Zhou, Jinchun; Ward, E. Sally (2004-02-15). "Visualizing the Site and Dynamics of IgG Salvage by the MHC Class I-Related Receptor, FcRn". The Journal of Immunology. 172 (4): 2021–2029. doi:10.4049/jimmunol.172.4.2021. ISSN 0022-1767.
  17. ^ Ober, Raimund J.; Martinez, Cruz; Lai, Xuming; Zhou, Jinchun; Ward, E. Sally (2004-07-27). "Exocytosis of IgG as mediated by the receptor, FcRn: An analysis at the single-molecule level". Proceedings of the National Academy of Sciences. 101 (30): 11076–11081. doi:10.1073/pnas.0402970101. PMC 503743. PMID 15258288.
  18. ^ Ward, E. Sally; Martinez, Cruz; Vaccaro, Carlos; Zhou, Jinchun; Tang, Qing; Ober, Raimund J. (April 2005). "From Sorting Endosomes to Exocytosis: Association of Rab4 and Rab11 GTPases with the Fc Receptor, FcRn, during Recycling". Molecular Biology of the Cell. 16 (4): 2028–2038. doi:10.1091/mbc.e04-08-0735. ISSN 1059-1524.
  19. ^ a b Ghetie, Victor; Popov, Serguei; Borvak, Jozef; Radu, Caius; Matesoi, Diana; Medesan, Corneliu; Ober, Raimund J.; Ward, E. Sally (July 1997). "Increasing the serum persistence of an IgG fragment by random mutagenesis". Nature Biotechnology. 15 (7): 637–640. doi:10.1038/nbt0797-637. ISSN 1546-1696.
  20. ^ "Ultomiris (ravulizumab-cwvz) FDA Approval History". Drugs.com. Retrieved 2025-09-30.
  21. ^ Commissioner, Office of the (2024-08-09). "FDA Approves New Drug to Prevent RSV in Babies and Toddlers". FDA. Retrieved 2025-09-30.
  22. ^ a b Vaccaro, Carlos; Zhou, Jinchun; Ober, Raimund J.; Ward, E. Sally (October 2005). "Engineering the Fc region of immunoglobulin G to modulate in vivo antibody levels". Nature Biotechnology. 23 (10): 1283–1288. doi:10.1038/nbt1143. ISSN 1546-1696.
  23. ^ Commissioner, Office of the (2024-08-09). "FDA Approves New Treatment for Myasthenia Gravis". FDA. Retrieved 2025-09-30.
  24. ^ "Advancing Health through Innovation: New Drug Therapy Approvals 2021". U.S. Food and Drug Administration. 2022-05-13. Archived from the original on 2022-12-06. Retrieved 2025-09-30.
  25. ^ "More than two decades of UTSW research paves way for first-in-kind drug". utsouthwestern.edu. 3 January 2022. Retrieved 2022-05-11.
  26. ^ a b Devanaboyina, Siva Charan; Khare, Priyanka; Challa, Dilip K.; Ober, Raimund J.; Ward, E. Sally (2017-05-31). "Engineered clearing agents for the selective depletion of antigen-specific antibodies". Nature Communications. 8 (1) 15314. doi:10.1038/ncomms15314. ISSN 2041-1723. PMC 5460014. PMID 28561044.
  27. ^ a b Kang, Jeffrey C.; Sun, Wei; Khare, Priyanka; Karimi, Mostafa; Wang, Xiaoli; Shen, Yang; Ober, Raimund J.; Ward, E. Sally (2019-04-01). "Engineering a HER2-specific antibody–drug conjugate to increase lysosomal delivery and therapeutic efficacy". Nature Biotechnology. 37 (5): 523–526. doi:10.1038/s41587-019-0073-7. ISSN 1546-1696. PMC 6668989. PMID 30936563.
  28. ^ "Sally Ward | VIB Conferences". www.vibconferences.be. Archived from the original on 2021-04-18. Retrieved 2025-10-02.
  29. ^ "Professor Sally Ward | University of Southampton". University of Southampton. Archived from the original on 2025-10-02. Retrieved 2025-10-02.
  30. ^ "Sally Ward, Ph.D." The Antibody Society. Archived from the original on 2025-08-15. Retrieved 2025-10-02.
  31. ^ "Professor Sally Ward wins international prize for breakthroughs in antibody therapies". www.southampton.ac.uk. Archived from the original on 2025-10-02. Retrieved 2025-10-02.
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