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Laboratory of Cell Therapy and Cancer Vaccine

Research lead:​A/Prof Han Chong TOH
Research team:

​Dr Who-Whong WANG

Dr Timothy SHUEN

Dr See Voon SEOW 


Chit Lai CHEE 

Lip Seng KOH 

Charmaine TAN 

Janice LIM 

Rachael CHEONG 

Rebecca BA 


Siew Kuen HEW 


Lay Hoon LEE 

Esther NA

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Bioimaging Consortium (SBIC), we have developed novel immunocompetent GATA4-deficiency liver cancer mouse models [unpublished], novel humanised HCC mouse models, as well as uncovered key metabolic pathways related to HCC tumorigenesis.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.

Selected publications

  1. Tay RE, Richardson EK, Toh HC. Revisiting the role of CD4+ T cells in cancer immunotherapy-new insights into old paradigms. Cancer Gene Ther. 2021 Feb;28(1-2):5-17. doi: 10.1038/s41417-020-0183-x. Epub 2020 May 27. PMID: 32457487; PMCID: PMC7886651. 
  2. Han S, Shuen T, Wang WW, Nazim E, Toh HC. Tailoring precision immunotherapy: coming to a clinic soon? ESMO Open. 2020;5 Suppl 1(Suppl 1): e000631. doi: 10.1136/esmoopen-2019-000631. Epub 2020 Sep 30. PMID: 33558033; PMCID: PMC7046383. 
  3. Chong YC, Toh TB, Chan Z, Lin QXX, Thng DKH, Hooi L, Ding Z, Shuen T, Toh HC, Dan YY, Bonney GK, Zhou L, Chow P, Wang Y, Benoukraf T, Chow EK, Han W. 2020 Targeted Inhibition of Purine Metabolism Is Effective in Suppressing Hepatocellular Carcinoma Progression. Hepatol Commun. Jul 27;4(9):1362-1381. doi: 10.1002/hep4.1559. PMID: 32923839; PMCID: PMC7471427. 
  4. Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. doi: 10.1056/NEJMoa1915745. PMID: 32402160. 
  5. Ding Z, Ericksen RE, Escande-Beillard N, Lee QY, Loh A, Denil S, Steckel M, Haegebarth A, Shuen T, Chow P, Toh HC, Reversade B, Gruenewald S, Han W. 2020. Metabolic pathway analyses identify proline biosynthesis pathway as a promoter of liver tumorigenesis. J Hepatol. 2020 Apr;72(4):725-735. doi: 10.1016/j.jhep.2019.10.026. Epub 2019 Nov 11. PMID: 31726117. 
  6. Hopkins R, Xiang W, Marlier D, Au VB, Ching Q, Wu LX, Guan R, Lee B, Chia WK, Wang WW, Wee J, Ng J, Cheong R, Han S, Chu A, Chee CL, Shuen T, Podinger M, Lezhava A, Toh HC^, Connolly JE^. Monocytic Myeloid-Derived Suppressor Cells Underpin Resistance to Adoptive T Cell Therapy in Nasopharyngeal Carcinoma. Mol Ther. 2021 Feb 3;29(2):734-743. doi: 10.1016/j.ymthe.2020.09.040. Epub 2020 Sep 30. PMID: 33038324; PMCID: PMC7854281. (^co-corresponding authors) 
  7. Ericksen RE, Lim SL, McDonnell E, Shuen T, Vadiveloo M, White PJ, Ding Z, Kwok R, Lee P, Radda GK, Toh HC, Hirschey MD, Han W. 2019. Loss of BCAA Catabolism during Carcinogenesis Enhances mTORC1 Activity and Promotes Tumor Development and Progression. Cell Metab. 2019 May 7;29(5):1151-1165.e6. doi: 10.1016/j.cmet.2018.12.020. Epub 2019 Jan 17. PMID: 30661928; PMCID: PMC6506390.
  8. Zhao Y, Shuen T, Toh TB, Chan XY, Liu M, Tan SY, Fan Y, Yang H, Lyer SG, Bonney GK, Loh E, Chang KTE, Tan TC, Zhai W, Chan JKY, Chow EK, Chee CE, Lee GH, Dan YY, Chow PK, Toh HC, Lim SG, Chen Q. 2018. Development of a new patient-derived xenograft humanised mouse model to study human-specific tumour microenvironment and immunotherapy. Gut. 2018 Oct;67(10):1845-1854. doi: 10.1136/gutjnl-2017-315201. Epub 2018 Mar 30. PMID: 29602780; PMCID: PMC6145285. 
  9. Enane FO*, Shuen T*, Gu X, Quteba E, Przychodzen B, Makishima H, Bodo J, Ng J, Chee CL, Ba R, Seng Koh L, Lim J, Cheong R, Teo M, Hu Z, Ng KP, Maciejewski J, Radivoyevitch T, Chung A, Ooi LL, Tan YM, Cheow PC, Chow P, Chan CY, Lim KH, Yerian L, Hsi E, Toh HC^, Saunthararajah Y^. 2017. GATA4 loss of function in liver cancer impedes precursor to hepatocyte transition. J Clin Invest. 2017 Sep 1;127(9):3527-3542. doi: 10.1172/JCI93488. Epub 2017 Jul 31. PMID: 28758902; PMCID: PMC5669578. (*co-first authors, ^co-corresponding authors) 
  10. Cainap C, Qin S, Huang WT, Chung IJ, Pan H, Cheng Y, Kudo M, Kang YK, Chen PJ, Toh HC, Gorbunova V, Eskens FA, Qian J, McKee MD, Ricker JL, Carlson DM, El-Nowiem S. Linifanib versus Sorafenib in patients with advanced hepatocellular carcinoma: results of a randomized phase III trial. J Clin Oncol. 2015 Jan 10;33(2):172-9. doi: 10.1200/JCO.2013.54.3298. Epub 2014 Dec 8. Erratum in: J Clin Oncol. 2017 Aug 1;35(22):2590. PMID: 25488963; PMCID: PMC4279237. 
  11. Bard-Chapeau EA, Nguyen AT, Rust AG, Sayadi A, Lee P, Chua BQ, New LS, de Jong J, Ward JM, Chin CK, Chew V, Toh HC, Abastado JP, Benoukraf T, Soong R, Bard FA, Dupuy AJ, Johnson RL, Radda GK, Chan EC, Wessels LF, Adams DJ, Jenkins NA, Copeland NG. Transposon mutagenesis identifies genes driving hepatocellular carcinoma in a chronic hepatitis B mouse model. Nat Genet. 2014 Jan;46(1):24-32. doi: 10.1038/ng.2847. Epub 2013 Dec 8. PMID: 24316982; PMCID: PMC4131144. 
  12. Chia WK, Teo M, Wang WW, Lee B, Ang SF, Tai WM, Chee CL, Ng J, Kan R, Lim WT, Tan SH, Ong WS, Cheung YB, Tan EH, Connolly JE, Gottschalk S, Toh HC. Adoptive T-cell transfer and chemotherapy in the first-line treatment of metastatic and/or locally recurrent nasopharyngeal carcinoma. Mol Ther. 2014 Jan;22(1):132-9. doi: 10.1038/mt.2013.242. Epub 2013 Oct 17. PMID: 24297049; PMCID: PMC3978790. 
  13. Chia WK, Wang WW, Teo M, Tai WM, Lim WT, Tan EH, Leong SS, Sun L, Chen JJ, Gottschalk S, Toh HC. A phase II study evaluating the safety and efficacy of an adenovirus-ΔLMP1-LMP2 transduced dendritic cell vaccine in patients with advanced metastatic nasopharyngeal carcinoma. Ann Oncol. 2012 Apr;23(4):997-1005. doi: 10.1093/annonc/mdr341. Epub 2011 Aug 4. PMID: 21821548; PMCID: PMC3314324. 
  14. Chia WK, Ali R, Toh HC. Aspirin as adjuvant therapy for colorectal cancer--reinterpreting paradigms. Nat Rev Clin Oncol. 2012 Oct;9(10):561-70. doi: 10.1038/nrclinonc.2012.137. Epub 2012 Aug 21. PMID: 22910681. 
  15. Chew V, Tow C, Teo M, Wong HL, Chan J, Gehring A, Loh M, Bolze A, Quek R, Lee VK, Lee KH, Abastado JP, Toh HC^, Nardin A^. Inflammatory tumour microenvironment is associated with superior survival in hepatocellular carcinoma patients. J Hepatol. 2010 Mar;52(3):370-9. doi: 10.1016/j.jhep.2009.07.013. Epub 2009 Aug 3. PMID: 19720422. (^co-corresponding authors) 
  16. Toh HC, Wang WW, Chia WK, Kvistborg P, Sun L, Teo K, Phoon YP, Soe Y, Tan SH, Hee SW, Foo KF, Ong S, Koo WH, Zocca MB, Claesson MH. Clinical Benefit of Allogeneic Melanoma Cell Lysate-Pulsed Autologous Dendritic Cell Vaccine in MAGE-Positive Colorectal Cancer Patients. Clin Cancer Res. 2009 Dec 15;15(24):7726-7736. doi: 10.1158/1078-0432.CCR-09-1537. PMID: 19996212.