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Immune Cell Manufacturing

Immune Cell Manufacturing

Enabling production of tomorrow's cellular immunotherapies

The Immune Cell Manufacturing group focuses on developing bioprocesses for manufacturing and in-depth characterisation of autologous and allogeneic cellular immunotherapies against cancer. Our research activities encompass engineering of feeder cells, design of workflows and optimization of media to promote expansion of NK and T cells with enhanced functional potency and durability. These cells may be modified with chimeric antigen receptors (CARs) to improve cancer targeting or gene-edited to overcome therapy resistance.


Focus Areas

  • Process development for manufacturing of allogeneic NK/T cells
  • Process development for manufacturing of autologous CAR-T therapies
  • Immunotherapy against solid tumours
  • Derivation of stem cells for cultivated meat production
  • Analytical assessment of mRNA-based therapeutics and prophylactics


Cellular Immunotherapies

DEVELOPMENT OF PRE-GMP PROCESSES

DEVELOPMENT OF PRE-GMP PROCESSES

CAR delivery to engineer immune cells, media development, feeder cell and viral vector production, process scale-up

CAR Engineering

CAR ENGINEERING

Rational design to enable enhanced killing efficacy and functional persistence against solid tumours

FEEDER CELL LINE ENGINEERING

FEEDER CELL LINE ENGINEERING

Supporting expansion of allogeneic NK / T cells with enhanced anti-tumour function

ALLOGENEIC CELLULAR IMMUNOTHERAPIES

ALLOGENEIC CELLULAR IMMUNOTHERAPIES

Process development for manufacturing “off-the-shelf” immunotherapy products

VIRAL VECTOR PRODUCTION

VIRAL VECTOR PRODUCTION

Lab-scale production of CAR virus-producing cells (VPCs) and CAR retroviral vectors (RVVs)

COMPREHENSIVE INSIGHTS NK T CELL PRODUCTION

COMPREHENSIVE INSIGHTS: NK/T CELL PRODUCTION

Identification of critical process parameters (CPPs) and critical quality attributes (CQAs) to characterise cells of high quality

From CAR delivery and feeder cell line engineering, to viral vector production, we are developing an integrated platform to meet your end-to-end needs in the development of pre-GMP processes for manufacturing of high-quality cellular immunotherapies.


Manufacturing of Cellular Immunotherapies

PD of Manufactg of Autologous CAR-T 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

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

Isolation and in vitro culture of stem cells for cultivated seafood

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

Analytical testing of mRNA-based therapeutics and prophylactics
  • 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
* Equal first author

The Team

Andy Tan

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
alison lee

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
Chelsia Wang

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
Yang Lei

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
Yu Zhao

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
Danai Georgiadou2

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
Samantha Nguee

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

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