Laboratory of Cell Therapy and Cancer Vaccine

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Our laboratory is mainly involved in cancer immunology and immunotherapy for solid cancers. We have developed clinical cell-based immunotherapeutic strategies, including dendritic cell vaccines and adoptive transfer of Epstein Barr Virus (EBV)-specific T cells, and successfully completed immunotherapy clinical trials for colorectal cancer and EBV-associated cancer, nasopharyngeal carcinoma (NPC). For example, our published phase II clinical trial of autologous EBV-specific T cell treatment in 38 advanced NPC patients— showed very encouraging clinical benefit and survival outcomes, and this led to a collaboration with a Singaporean biotechnology company, Tessa Therapeutics, to embark on an FDA IND international multi-centre randomised phase III clinical trial in 330 NPC patients across 30 sites in 5 countries. In collaboration with a U.S. biotech company, we have also recently completed a first-in-human phase I trial of Ad-sig-hMUC-1/ecdCD40L cancer vaccine in epithelial cancers, including lung, breast, colon, ovary, and prostate cancers. Our laboratory is also a participant in a phase III randomised, open-label study comparing Pexa-Vec (vaccinia GMCSF/thymidine kinase-deactivated virus) followed by Sorafenib versus Sorafenib alone in patients with advanced hepatocellular carcinoma (HCC). Another ongoing effort is in the pre-clinical development of novel gamma-delta T (gdT) lymphocyte-based immunotherapy strategies, for which a patent has been filed for a proprietary GMP gdT cell production method.

Another key focus of our laboratory is to develop novel treatment strategies against HCC, focusing on gaining a deeper understanding of the interaction between the tumour and the immune system to more rationally design effective combination immunotherapies. GATA4, is a key gene that we have reported as central to oncogenesis. We are elucidating the biological pathways associated with GATA4 and its influence on the tumour microenvironment to uncover potential anti-cancer targets related to this central transcription factor. We have been awarded more than four national grants in past 4 years to establish new 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.

Selected publications

1. Zhao Y, Shuen TWH, Toh TB, et al. Development of a new patientderived
   xenograft humanised mouse model to study human-specific tumour microenvironment and immunotherapy. Gut. 2018. doi: 10.1136/ gutjnl-2017-315201.
2. Enane F, Shuen WH, Gu XR, et al. Genetic disruption of GATA4-mediated transactivation in liver cancer suppresses precursor to hepatocyte transition. J Clin Invest. 2017 Sep 1;127(9):3527-3542.
3. Chew V, Lai L, Pan L, et al. Delineation of an immunosuppressive gradient
   in hepatocellular carcinoma using high-dimensional proteomic and transcriptomic analyses. Proc Natl Acad Sci U S A. 2017;114:E5900–E5909.
4. Garnelo M, Tan A, Her Z, et al. Interaction between tumour-infiltrating B cells
   and T cells controls the progression of hepatocellular carcinoma. Gut. 2017
   Feb;66(2):342–351.
5. Garnelo M, Tan A, Her Z, et al. Interaction between tumour-infiltrating B cells
   and T cells controls the progression of hepatocellular carcinoma. Gut. 2017
   Feb;66(2):342-–351.