.png?sfvrsn=1a7df424_3)
Cellular Immunotherapies
DEVELOPMENT OF PRE-GMP PROCESSES
Car Engineering
FEEDER CELL LINE ENGINEERING
ALLOGENEIC CELLULAR IMMUNOTHERAPIES
VIRAL VECTOR PRODUCTION
COMPREHENSIVE INSIGHTS: NK/T CELL PRODUCTION
Manufacturing of Cellular Immunotherapies
Autologous alpha beta T cells
- Platform for CAR engineering and expansion: CAR engineering of ab T cells and their expansion utilising suitable bioreactors to generate pre-GMP bank from different donors.
- Immunophenotypic and functional characterisation: To investigate anti-tumour function and functional persistence or exhaustion of cells via flow cytometric and bioluminescence methods.
Allogeneic NK or gamma delta T cells
- Allogeneic Production: HLA-Unrestricted: NK / gd T cells derived from cord / peripheral blood, modified or not with CAR and expanded
- Enhanced expansion and anti-tumour potency: Engineering of feeder cells to provide specific signals that stimulate expansion of NK / gd T cells co-cultured with irradiated feeder cells
- Tumour-targeting efficiency: Transduction of NK / gd T cells with rationally designed CARs
- Clinically relevant numbers: GMP-compliant processes used to generate allogeneic cell products
- Efficient product assessment: Collaboration with other teams to establish CQAs of final product that positively correlate with its functional efficacy
- Clinical translation: Pre-GMP banking of CAR VPCs / RVVs, engineered feeder cells, CAR-NK / T cells
Cultivated Meat
Our work is part of CRISP Meats, an ongoing multi-institutional programme funded by the Singapore Food Story R&D Programme to develop novel technologies for the production of cultivated meat through public-private partnerships.
Our work includes:
- Isolation of stem cells from various animal species
- Optimisation of culture conditions
- Immortalisation of cells
- Characterisation of cell lines
Messenger RNA
- Develop and validate analytical methods: For characterising the identity, purity and potency of mRNA-based therapeutics which complement capabilities in mRNA manufacturing
Our Track Record
Featured publications:
- Chelsia Qiuxia Wang, Fong Chan Choy, Arleen Sanny, Takashi Murakami, Andy Hee-Meng Tan & Kong-Peng Lam (2023) An Inhibitory Role for Human CD96 Endodomain in T Cell Anti-Tumor Responses. Cells 12: 309
- Zhenzhong Chen*, Seokgyu Han*, Arleen Sanny, Dorothy Leung-Kwan Chan, Danny van Noort, Wanyoung Lim, Andy Hee-Meng Tan & Sungsu Park (2022) 3D hanging spheroid plate for high-throughput CAR T cell cytotoxicity assay. Journal of Nanobiotechnology 20: 1–14
- Andy Hee-Meng Tan, Alice Man Sze Cheung & Dieter Kabelitz (2022) Editorial: Next generation gd T cell-based tumor immunotherapy. Frontiers in Immunology 13: 1041362
- Chelsia Qiuxia Wang & Andy Hee-Meng Tan (2021) Driving CARs on the biomanufacturing road to clinical success. Cell and Gene Therapy Insights 7: 1613–1621
- Alison P Lee*, Yee Jiun Kok*, Meiyappan Lakshmanan*, Dawn Leong, Lu Zheng, Hsueh Lee Lim, Shuwen Chen, Shi Ya Mak, Kok Siong Ang, Neil Templeton, Taha Salim, Xiaona Wei, Eric Gifford, Andy Hee-Meng Tan, Xuezhi Bi, Say Kong Ng, Dong-Yup Lee, Wai Lam W Ling & Ying Swan Ho (2021) Multi-omics profiling of a CHO cell culture system unravels the effect of culture pH on cell growth, antibody titer, and product quality. Biotechnology and Bioengineering 118(11): 4305–4316
The Team
Dr Andy Tan
andy_tan@bti.a-star.edu.sg
Principal Scientist II
PhD in Immunology (2008), National University of Singapore Graduate School for Integrative Sciences and Engineering, Singapore
Research Focus / Interest
- Process development for manufacturing of autologous and allogeneic cellular immunotherapies
- Development of cell lines from food animal species for cultivated meat applications
- Nucleic Acid- and Immuno-Analytics for characterisation of RNA prophylactics and therapeutics
Dr Alison Lee
alison_lee@bti.a-star.edu.sg
Principal Scientist I
PhD in Bioinformatics (2009), NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore
Research Focus / Interest
- Transcriptomics and epigenomics of cell factories of biotechnological interest such as Chinese Hamster Ovary (CHO) cell lines to identify crucial regulatory networks influencing product quality and yield
- Cultivated meat production and safety assessment
- mRNA characterisation and analysis
Dr Chelsia Wang
chelsia_wang@bti.a-star.edu.sg
Senior Scientist II
PhD in Biological Sciences (2012), National University of Singapore, Singapore
Research Focus / Interest
- Process development for manufacturing of autologous and allogeneic cellular immunotherapies
- Therapies targeting solid tumours and leukemias
Dr Esmond Lee
esmond_lee_yan_zhao@bti.a-star.edu.sg
Senior Scientist I
PhD in Stem Cell Biology & Regenerative Medicine (2022), Stanford University, USA
Research Focus / Interest
- Study of immune tolerance in health and disease, engineer Regulatory T cells to alleviate autoimmune disease and enable transplantation tolerance
- Combining knowledge of immune cell biology and machine learning approaches for process development in cell therapy manufacturing
Dr Yang Lei
yang_lei@bti.a-star.edu.sg
Senior Scientist I
PhD in Immunology (2019), National University of Singapore, Singapore
Research Focus / Interest
- Cancer immunotherapy
- Translational research
Dr Zhao Yu
yu_zhao@bti.a-star.edu.sg
Senior Scientist I
PhD in Pharmacology (2010), Academy of Military Medical Science, China
Research Focus / Interest
- Investigation and Development cellular/genetic therapeutic products for anti-tumor therapy
- The interaction and regulatory network between tumour microenvironment and immune cells in the solid tumours
- Process development and optimization of cellular/genetic therapeutic products manufacturing
Dr Danai Georgiadou
danai_georgiadou@bti.a-star.edu.sg
Scientist
PhD in Human Development and Embryology (2022), University of Amsterdam, The Netherlands
Research Focus / Interest
- Investigating the influence of diverse culture conditions and growth factors on the development of high-quality cultivated meat cell lines
- Understanding the interactions between different cell types in tissues from various species for improved functionality and growth
- Exploring the viability and scalability of alternative cell sources for cultivated meat production
- Employing stem cell-based methodologies to augment the efficiency and productivity of primary cell isolation processes
Dr Samantha Nguee
samantha_nguee@bti.a-star.edu.sg
Scientist
PhD in Microbiology and Immunology (2021), Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Research Focus / Interest
- Process development for manufacturing of cellular immunotherapies
- Optimization and validation of cellular immunotherapies
Dr Toh Jia Ying
toh_jia_ying@bti.a-star.edu.sg
Scientist
PhD in Immunology (2023), Stanford University, United States of America
Research Focus / Interest
- Development and optimisation of manufacturing processes for allogeneic cellular immunotherapies against cancer
- Immunophenotyping and characterisation of cellular immunotherapy products
