Dr Who-Whong WANG
Dr Timothy SHUEN
Dr See Voon SEOW
Dr Emma Kay RICHARDSON
Chit Lai CHEE
Lip Seng KOH
Hui Shi CHEONG
Siew Kuen HEW
Lay Hoon LEE
Our laboratory focuses primarily on cancer immunology and immunotherapy for solid tumours, including better understanding their mechanisms of resistance and efficacy. We have developed clinical cell-based immunotherapeutic strategies, including dendritic cell vaccines and adoptive transfer of Epstein Barr Virus (EBV)-specific T cells, and completed cancer vaccine clinical trials against advanced colorectal cancer and nasopharyngeal carcinoma (NPC). Our phase II clinical trial of autologous EBV-specific T cell therapy following chemotherapy in 38 advanced NPC patients - showed encouraging clinical benefit and survival outcomes. This led to a close partnership with Singapore biotechnology company, Tessa Therapeutics Ltd, to embark on an FDA IND international multi-centre randomised phase III clinical trial in 330 NPC patients across 30 sites in 5 countries. We recently completed a first-in-human phase I trial of Ad-sig-hMUC-1/ecdCD40L cancer vaccine in epithelial cancers. We are developing novel gamma-delta T (gdT) and other cellular immunotherapy strategies. Our translational research area pivots on such immunotherapies to identify predictive transcriptomic-based and cellular biomarkers using single-cell transcriptomics (scRNA-Seq), Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq), mass cytometry etc.
Another key focus of our laboratory is to study the biology and identify novel treatment strategies against HCC, focusing on gaining a deeper understanding of the interaction between the tumour and the immune microenvironment including the study of novel immune checkpoints. GATA4, is a key transcription gene that we reported as central to oncogenesis when a copy of GATA4 is deleted. We are elucidating the biological pathways associated with GATA4 and its loss. In collaboration with A*STAR institutions including Genome Institute of Singapore (GIS), Singapore Immunology Network (SIgN), Institute of Molecular & Cell Biology (IMCB), Singapore Bioimaging Consortium (SBIC), we have developed novel immunocompetent GATA4-deficiency liver cancer mouse models [unpublished], novel humanised HCC mouse models, as well as uncovered key metabolic pathways related to HCC tumorigenesis. Another focus area is the establishment of in vitro 3D systems including organoids to more deeply interrogate HCC biology and for therapeutic targeting.
In the past 5 years, we have been awarded more than four national grants to establish the in vitro and in vivo liver cancer models to delineate the molecular mechanisms of GATA4, to investigate the genomic and immune heterogeneity in HCC, and to rationally design and test new combination immunotherapies for treatment in HCC. We are actively studying EBV epithelial cancers in depth also. We have been awarded the NMRC Open Fund – Large Collaborative Grant (OF-LCG) to support our national programme: the Virus-Induced Cancers: Translational Oncology Research and immunologY (VICTORY) consortium, with major emphases on translational biology, immunology and immunotherapy targeting of EBV, HPV, and HBV/HCV-related cancers.
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