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Improved manufacturing of CD19 and novel TIM3-targeted CAR-T cells for acute myeloid leukaemia

Purpose

Improved manufacturing of CD19 and novel TIM3-targeted CAR-T cells for acute myeloid leukaemia

Crosscut Captains

Michael Birnbaum

Associate Professor of Biological Engineering, MIT

While CAR-T therapies are transforming the landscape of cancer treatment, multiple hurdles have limited the impact even of FDA approved therapies. As genetically modified autologous cell therapies, CAR-T treatments are notoriously expensive (often exceeding US$500,000/dose), and are beset with manufacturing challenges. For CAR-T cells to mature as therapies, improvements must be made for the discovery and detection of attributes for potency and safety, sterility testing, control of processes, and time to manufacture. At CAMP, we are working on technologies to improve each aspect of CAR-T manufacturing, from the discovery and detection of functional attributes, to improved testing of adventitious agents, to improved means of growing the cells themselves.

Highlights

SMART CAMP Researchers Pioneer Production of CAR T-Cells Using High-Density Microfluidic Bioreactor

This is the first demonstration of T-cell culture in a microfluidic chip the size of a pack of cards, allowing the miniaturisation of CAR T-cell production for cancer treatment.

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New contamination-detection test to improve T-cell therapy

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Media/Press Release

Generation Next: New Era of Excellence

PORTFOLIO highlights "Get To Know" individuals, who are ushering a new era of excellence in Singapore

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Cancer Cell Therapy: Looking to the Future of CAR T Cell Manufacturing

Manufacturing innovations in CAR T cell therapies could be a game-changer for many late-stage cancer patients.

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Publications

Ri Lu (NUS), Yan Shan Ang (NUS), Ka-Wai Cheung (SMART), Kai Yun Quek (SMART), Wei-Xiang Sin (SMART), Elizabeth Lee (SMART), Shir Lynn Lim (NUS), Lin-Yue Lanry Yung (NUS), Michael E. Birnbaum (MIT/SMART), Jongyoon Han (MIT/SMART), Lih Feng Cheow (NUS), Kerwin Kwek Zeming (SMART)

iSECRETE: Integrating Microfluidics and DNA Proximity Amplification for Synchronous Single-Cell Activation and IFN-𝜸 Secretion Profiling

Adv. Sci. 2024, 2309920; Aug 22, 2024

2024

SMART CAMP Authors

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Hyungkook Jeon (MIT), Caleb R. Perez (MIT/SMART), Taeyoon Kyung (MIT), Michael E. Birnbaum (MIT/SMART), and Jongyoon Han (MIT/SMART)

Separation of Activated T Cells Using Multidimensional Double Spiral (MDDS) Inertial Microfluidics for High-Efficiency CAR T Cell Manufacturing

Analytical Chemistry; Jun 18, 2024

2024

SMART CAMP Authors

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Wei-Xiang Sin (SMART), N. Suhas Jagannathan (SMART), Denise Bei Lin Teo (SMART), Faris Kairi (SMART), Shin Yie Fong (ASTAR-IMCB), Joel Heng Loong Tan (ASTAR-IMCB), Dedy Sandikin (SMART), Ka-Wai Cheung (SMART), Yen Hoon Luah (SMART), Xiaolin Wu (SMART), Joshua Jebaraj Raymond (SMART), Francesca Lorraine Wei Inng Lim (ACTRIS/SGH), Yie Hou Lee (SMART), Michaela Su-Fern Seng (SingHealth), Shui Yen Soh (SingHealth), Qingfeng Chen (ASTAR-IMCB), Rajeev J. Ram (SMART/MIT), Lisa Tucker-Kellogg (Duke-NUS) & Michael E. Birnbaum (SMART/MIT)

A high-density microfluidic bioreactor for the automated manufacturing of CAR T cells

Nature Biomedical Engineering, Published online; Jun 04, 2024

2024

SMART CAMP Authors

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Khloe S. Gordon, Taeyoon Kyung, Caleb R. Perez, Patrick V. Holec, Azucena Ramos, Angela Q. Zhang, Yash Agarwal, Yunpeng Liu, Catherine E. Koch, Alina Starchenko, Brian A. Joughin, Douglas A. Lauffenburger, Darrell J. Irvine, Michael T. Hemann & Michael E. Birnbaum

Screening for CD19-specific chimaeric antigen receptors with enhanced signalling via a barcoded library of intracellular domains`

Nature Biomedical Engineering, 6, pp. 855–866; Jun 16, 2022

2022

SMART CAMP Authors

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Connor S Dobson, Anna N. Reich, Stephanie Gaglione, Blake E. Smith, Ellen J. Kim , Jiayi Dong, Larance Ronsard, Vintus Okonkwo, Daniel Lingwood, Michael Dougan , Stephanie K. Dougan & Michael E. Birnbaum

Antigen identification and high throughput interaction mapping by reprogramming viral entry

Nature Methods, 19, pp. 449-460; Apr 08, 2022

2022

SMART CAMP Authors

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Kerwin Kwek Zeming, Rohan Vernekar, Mui Teng Chua, Kai Yun Quek, Greg Sutton, Timm Krüger, Win Sen Kuan, Jongyoon Han

Label‐Free Biophysical Markers from Whole Blood Microfluidic Immune Profiling Reveal Severe Immune Response Signatures

Small, 17 (12), 2006123; Mar 25, 2021

2021

SMART CAMP Authors

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Kerwin Kwek Zeming, Ri Lu, Kai Lee Woo, Guoyun Sun, Kai Yun Quek, Lih Feng Cheow, Chia-Hung Chen, Jongyoon Han, and Shir Lynn Lim

Multiplexed Single-Cell Leukocyte Enzymatic Secretion Profiling from Whole Blood Reveals Patient-Specific Immune Signature

Analytical Chemistry, 93 (10), pp. 4374–4382; Feb 18, 2021

2021

SMART CAMP Authors

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Conference Presentations

Yanmeng Yang (SMART), Nicholas Tan (SMART), Meiqi Kang (SMART), Mengli Chen (NUS), Liang Cui (SMART), Francesca Lorraine Wei Inng Lim (SingHealth), Yunxin Chen (SGH), Kerwin Kwek Zeming (SMART), Jongyoon Han (MIT/SMART)

"Rapid and Sensitive Determination of Iron in Biological Samples by Micro-magnetic Resonance Relaxometry (MRR) ", Cold Spring Harbor Asia conference on Frontiers in Iron, Reactive Oxygen Species & Ferroptosis in Life, Death & Disease in Suzhou, Nov 03, 2024-Nov 08, 2024, China

SMART CAMP Authors

2024

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Sin, WX. (SMART), Jagannathan, N.S.(SMART, Duke-NUS), Teo, D.B.L. (SMART), Kairi F. (SMART), Fong S.Y. (IMCB, A*STAR), Tan J.H.L.** (IMCB, A*STAR), Sandikin D. (SMART), Cheung K.W.** (SMART), Luah Y.H.** (SMART), Wu X.** (SMART), Raymond J.J. (SMART), Lim F.L.W.I. (SGH, SingHealth), Lee Y.H. (SMART), Seng M.S.F. (KKH, SingHealth), Soh S.Y. (KKH, SingHealth), Chen Q. (IMCB, A*STAR), Ram R.J. (MIT), Tucker-Kellogg L. (Duke-NUS), Birnbaum M.E. (MIT)

"A high-density microfluidic bioreactor for the automated manufacturing of CAR T cells", Singapore Cell and Gene Therapy Pan Asia Summit 2024, Jul 18, 2024-Sep 20, 2024, Singapore

SMART CAMP Authors

2024

External Link

Sin Wei-Xiang

"High-density microbioreactor process designed for automated point-of-care manufacturing of CAR T cells. ", ECI Advancing Manufacture of Cell and Gene Therapies VIII , Feb 04, 2024-Feb 08, 2024, Coronado, CA, USA

SMART CAMP Authors

2024

External Link

Wei-Xiang Sin, Narendra Suhas Jagannathan, Denise Bei Lin Teo, Faris Kairi, Dedy Sandikin, Ka-Wai Cheung, Yie Hou Lee, Rajeev J. Ram, Lisa Tucker-Kellogg, Michael E. Birnbaum

"High-density microbioreactor process designed for automated point-of-care manufacturing of CAR T cells", 15TH STEM CELL SOCIETY SINGAPORE SYMPOSIUM 2023; "STEM CELL INNOVATIONS IN RESEARCH AND HEALTHCARE", Nov 29, 2023-Dec 01, 2023, Singapore

SMART CAMP Authors

2023

External Link

Tan Kwan Zen Nicholas, Kwek Zeming Kerwin, Quek Kaiyun, Goh Chin Ren, Ng Zhi Heng Nicholas, Michael E. Birnbaum, Yunxin Chen, Francesca Lorraine Lim Wei Inng, Jongyoon Han

"Rapid assessment of immunological response in post-infusion CAR-T patients using biophysical WBC analysis", microTAS 2023, , Oct 15, 2023-Oct 19, 2023, Katowice, Poland

SMART CAMP Authors

2023

External Link

Nicholas Ng Zhi Heng, Kerwin Kwek Zeming, Kai Yun Quek, Francesca Loraine Lim, Yunxin Chen, Chin Ren Goh, Faye Cheung Ka Wai, Sin Wei Xiang, Michael E. Birnbaum, Jongyoon Han

"Rapid Label-Free Profiling and CAR-T Biophysical Morphologies for Continuous Monitoring", Singapore Cell & Gene Therapy Conference 2023, Aug 04, 2023-Aug 05, 2023, Singapore

SMART CAMP Authors

2023

External Link

Nicholas Tan Kwan Zen, Kerwin Kwek Zeming, Kai Yun Quek, Francesca Loraine Lim, Yunxin Chen, Chin Ren Goh, Nicholas Ng Zhi Heng, Michael E. Birnbaum, Jongyoon Han

"Rapid Assessment of immunological response in post-infusion CAR-T patients using biophysical WBC analysis", Singapore Cell & Gene Therapy Conference 2023, Aug 04, 2023-Aug 05, 2023, Singapore

SMART CAMP Authors

2023

External Link

Kerwin Kwek Zeming, Kai Yun Quek, Wei-Xiang Sin, Ka-Wai Cheung, Michael E. Birnbaum, Jongyoon Han

"Rapid Label-free Microfluidic Assay for Profiling Functional Phenotypes of CAR T Cells: Towards Enhanced Manufacturing Control", Singapore Cell & Gene Therapy Conference 2023, Aug 04, 2023-Aug 05, 2023, Singapore

SMART CAMP Authors

2023

External Link

James P. B. Strutt (SMART), Meenubharathi Natarajan (SMART), Wei Xiang Sin (SMART), Elizabeth Lee (SMART), Paul W. Barone (MIT), Jacqueline M. Wolfrum (MIT), Rohan B. H. Williams (NTU), Scott A. Rice (NTU), Stacy L. Springs (MIT)

"Machine-learning based detection of adventitious agents in T cell therapy cultures using long read sequencing", 14th Stem Cell Society Singapore Symposium 2022, Dec 07, 2022-Dec 09, 2022, Singapore

SMART CAMP Authors

2022

External Link

Wei-Xiang SIN (SMART), Denise TEO (SMART), Kevin S. LEE (Erbi Biosystems Inc), Harry LEE (Erbi Biosystems Inc), Narendra Suhas JAGANNATHAN (Duke-NUS), Rajeev RAM (MIT), Lisa TUCKER-KELLOGG (Duke-NUS), Michael BIRNBAUM (MIT)

"High Density CAR T Cell Culture with a 2-mL Continuous Perfusion Bioreactor", 14th Stem Cell Society Singapore Symposium 2022, Dec 07, 2022-Dec 09, 2022, Singapore

SMART CAMP Authors

2022

External Link

Wei-Xiang SIN (SMART), Faye CHEUNG (SMART), Sandy LEE (A*STAR SIgN), Dedy SANDIKIN (SMART), Denise TEO (SMART), Faris KAIRI (SMART), Cheng-I WANG (A*STAR SIgN), Michael BIRNBAUM (MIT)

"Characterization of LVV-Transduced, In Vitro-Expanded Anti-TIM3 CAR T Cells", 14th Stem Cell Society Singapore Symposium 2022, Dec 07, 2022-Dec 09, 2022, Singapore

SMART CAMP Authors

2022

External Link

Kevin S. Lee (Erbi Biosystems Inc.), Wei-Xiang Sin (SMART), Michael Birnbaum (MIT)

"Cell therapy process development with a 2 mL continuous perfusion bioreactor", 27th ESACT Meeting, Jun 26, 2022-Jun 29, 2022, Lisbon, Portugal

SMART CAMP Authors

2022

External Link

Wei-Xiang Sin (SMART), Kevin S. Lee (Erbi Biosystems Inc.), Harry Lee (Erbi Biosystems Inc.), Michael Birnbaum (MIT)

"High density CAR T cell culture with a 2 mL continuous perfusion bioreactor", SDCT-REMEDIS Cell Therapy Conference, Jun 23, 2022-Jun 24, 2022, Virtual (Singapore)

SMART CAMP Authors

2022

External Link

Wei-Xiang Sin

"Cell therapy process development with a 2 mL continuous perfusion bioreactor", A*STAR Advances in Cell and Gene Therapy (A*CGT) Symposium, May 11, 2022-Jun 12, 2022, Singapore

SMART CAMP Authors

2022

External Link

Kevin S. Lee (Erbi Biosystems Inc, Wei-Xiang Sin (SMART), Harry Lee (Erbi Biosystems Inc.), Michael Birnbaum (MIT)

"Erbi Biosystems - Cell culture development with a 2 mL continuous perfusion bioreactor", Advancing Manufacture of Cell and Gene Therapies VII, Engineering Conference International, Feb 06, 2022-Feb 10, 2022, Coronado, CA, USA

SMART CAMP Authors

2022

External Link

Bottleneck 1

There are no label-free methods of monitoring cell attributes during production (for rapid feedback), and it is not clear how predictive current attributes are.

Bottleneck 2

Processes are slow (weeks) and challenging to scale-out for autologous CAR T-cells; reagent innovations costly to evaluate for optimal manufacturing.

Goal 1

To identify rapid, (ideally) label-free CQAs for CAR T-cell potency and sterility.

Goal 2

To improve CAR-T production via deployment of new production technologiesand PATs.