Areas of Excellence

Centre for Medical Engineering of Molecular and Biological Probes

Total Funding Approved

• HK$71.161M

Indicative Project Time-Frame

• 2021-2029

Coordinating Institution

• The Chinese University of Hong Kong (Prof. Nathalie Wong)

Cell-surface proteins are the primary route of cell-cell and cell-environment communication, and an integral class of proteins that tightly regulates numerous cellular processes and vital signalling. Although membrane proteins represent only ~23% of the human proteome, over 60% of current FDA-approved drugs are directed against them. Despite their clinical appeal, cell-surface proteins are underrepresented in public proteome and genome databases. In this Project, we propose to conduct a systematic analysis for focused discoveries of cell-surface neo-epitopes in cancers widely found in Asia: hepatocellular carcinoma (HCC), nasopharyngeal carcinoma (NPC) and lung adenocarcinoma (LADC). We will leverage the information for generating dual-targeted theranostic probes for molecular imaging and precision therapy. We will also exploit characteristic features of cell-surface antigens for engineering genetically modified CAR T-cells.

To achieve our goals, we have assembled a multidisciplinary team of strong investigators. Our team members have previously made important discoveries on the causal events of HCC, NPC and LADC, yet establishing many of these somatic changes in tailored therapy remains a challenge due to the limited number of approved drugs in targeting genetic vulnerabilities. Our recent sequencing work has revealed a window for theranostics development by directing probes against tumor-specific cell-surface proteins. We have obtained evidence from SMRT sequencing to show that neojunctions derived from Alternative Splicing are vastly more common than somatic mutations, and many involved cell-surface receptors. This new knowledge has invigorated our pursuit of more promising treatment options and inspired the current application. Our team members have also made significant contributions in cell-SELEX screening for nucleic acid aptamers and characterized surface proteins for antigen-binding fragment in CAR T-cells engineering. We have successfully licensed diagnostic assays and founded biotech companies in Hong Kong. Furthermore, our clinical investigators are all frontline clinicians and leaders in international clinical trials. This project will build on existing strengths, in terms of our track record in cancer genome and EBV research, bioinformatics, aptamer chemistry, small molecule synthesis, CAR engineering, clinical expertise in oncology, as well as unique study models and infra-structure facilities that we have collectively acquired over the years. The establishment of a ‘Centre’ for theranostics engineering under the aegis of the AoE scheme will have strategic importance for Hong Kong. The numerous applications of theranostics engineering in the fields of biotechnology and biomedicine will bring economic benefits, societal impact and fresh thinking, heightening the international stature of Hong Kong as a leading centre of excellence.