Resurrecting ancestral sugars: a molecular archaeology approach to immunotherapy
Lead Research Organisation:
University of York
Department Name: Chemistry
Abstract
In the last decade the precision treatment of cancer has been revolutionised. Firstly by targeted delivery of potent small molecule drugs as antibody conjugates, and subsequently by innovative cancer immunotherapy strategies which coopt the patient's own immune system to fight the cancer. In this project we aim to harness aspects of both these field defining strategies, using chemical glycobiology to develop a completely novel 'molecular archaeology' approach to cancer immunotherapy, by resurrecting the biosynthetic pathway of an ancestral sugar which would initiate a change in the recognition of a cancer cell by the immune system from 'self' to 'non-self'. We will validate this approach by focussing on prostate cancer, which affects 1 in 8 men in the UK.
Organisations
Publications
Barber LJ
(2023)
Selectivity and stability of N-terminal targeting protein modification chemistries.
in RSC chemical biology
Keenan T
(2021)
A Tale of Two Bioconjugations: pH Controlled Divergent Reactivity of Protein a-oxo-Aldehydes in Competing a-oxo-Mannich and Catalyst-Free Aldol Ligations.
in ACS chemical biology
Yates N
(2022)
Catalyst-free site-selective cross-aldol bioconjugations
Yates N
(2022)
Catalyst-free site-selective cross-aldol bioconjugations
in Green Chemistry
Yates NDJ
(2023)
Preparation and Application of an Inexpensive a-Formylglycine Building Block Compatible with Fmoc Solid-Phase Peptide Synthesis.
in Organic letters
Yates NDJ
(2023)
Site-Selective Aryl Diazonium Installation onto Protein Surfaces at Neutral pH using a Maleimide-Functionalized Triazabutadiene.
in Chembiochem : a European journal of chemical biology
| Description | During this award we worked towards developing a new approach for cancer glyco-immunotherapy, specifically through the development of new gene delivery methods for targeting prostate cancer cells. We have established and published a new approach to targeting payloads to these cancer cells and in preliminary experiments shown that this platform system may be amenable to delivery of DNA. |
| Exploitation Route | A number of publications have arisen from the award detailing new methods for protein bioconjugation which may prove of utility in both academic and non academic settings, particularly in the future development of therapeutic protein bioconjugates. |
| Sectors | Chemicals |