Cancer

Overview

The SIgN Cancer program uses deep immunophenotyping via the SIgN Immunomonitoring Platform to identify the pathological immune mechanisms and signalling pathways underlying cancer and to discover new biomarkers to better predict cancer prognosis and treatment responses. Here, pre-clinical studies, such as in vivo targeting in xenograft and humanized mouse models, and the Human Monoclonal Antibodies Platform are driving the development of new biologics. The overall research objective of the Cancer program is to translate novel discoveries to the clinic, and perform clinical immunomonitoring, clinical trials monitoring and develop point-of-care screening platforms.

The Cancer program covers three main themes:

Cancer Metabolism: using metabolomics, fluxomics and metabolic targeting

Immunotherapy: based on CAR-T cells, human monoclonal antibodies, immune checkpoint inhibitors and protein scaffold biologics

Immunomonitoring: by deep immune-phenotyping, immunogenomics and studies of the immune repertoire

Principal Investigators involved include:

Subhra BISWAS
Jinmiao CHEN
Katja FINK
Florent GINHOUX
Anis LARBI
Evan NEWELL
Lai Guan NG
Michael POIDINGER
Ee Chee REN
Cheng-I WANG
Siew Cheng WONG
Pingyu ZHONG

Click here to visit the Principal Investigators page.

Research highlights

The data produced by researchers in this program is of high scientific excellence, as indicated by numerous successful publications in high impact journals including Science, Blood, Gut, Lancet Oncology and Nature Cell Biology (see below). Furthermore, the studies conducted by our researchers have health, economic and industrial impact. Examples of the translational research conducted, and novel discoveries and innovative technologies contributed by the program include:

• Immune-oncology antibodies targeting immune checkpoint inhibitors (licensed)
• Immuno-metabolic profiling in human cancer
• Humanized NOG mice models in cancer
• Human vaccine platform in cancer
• Immune-signatures for cancer and immunotherapy 

Based on such developments, partnerships with various industry partners have been successfully established, including EuChole Bio Pte. Ltd (local spin-off acquired by Tessa Therapeutics), Merck, CIEA Japan and others.

In addition, the Cancer program has established collaborations with several clinical partners for access to various cancer cohorts including: the National Cancer Center Singapore, the Duke-NUS Graduate Medical School and Singapore General Hospital (Singhealth) and the National University Health Systems.

The Cancer program has international collaborations with researchers including at: the Humanitas University Milan, Italy; the University of Washington, USA; the University of California, USA; the University of Minnesota, USA.

Key Publications

Fehlings M et al. Checkpoint blockade immunotherapy reshapes the high-dimensional phenotypic heterogeneity of murine intratumoural neoantigen-specific CD8+ T cells. Nat Commun. 2017.
Simoni Y et al. Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency. Immunity. 2016.
Saha S et al. Tumor-Associated Neutrophils Show Phenotypic and Functional Divergence in Human Lung Cancer. Cancer Cell. 2016. 
Lee Y et al. Rewiring macrophages for anti-tumour immunity. Nat Cell Biol. 2016.
Salmon H et al. Expansion and Activation of CD103(+) Dendritic Cell Progenitors at the Tumor Site Enhances Tumor Responses to Therapeutic PD-L1 and BRAF Inhibition. Immunity. 2016.
Tan WL, Jain A, Takano A, Newell EW, Iyer NG, Lim WT, Tan EH, Zhai W, Hillmer AM, Tam WL, Tan DS. Novel therapeutic targets on the horizon for lung cancer. Lancet Oncol. 2016.
Hanna RN et al. Patrolling monocytes control tumor metastasis to the lung. Science. 2015.
Biswas SK. Metabolic Reprogramming of Immune Cells in Cancer Progression. Immunity. 2015.
Shalova IN et al. Human Monocytes Undergo Functional Re-programming during Sepsis Mediated by Hypoxia-Inducible Factor-1α. Immunity. 2015.
Garnelo M et al. Interaction between tumour-infiltrating B cells and T cells controls the progression of hepatocellular carcinoma. Gut. 2015.
Chittezhath M et al. Molecular profiling reveals a tumor-promoting phenotype of monocytes and macrophages in human cancer progression. Immunity. 2014.

 Click here to visit the full SIgN Publications page.