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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
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.
Generation Next: New Era of Excellence
PORTFOLIO highlights "Get To Know" individuals, who are ushering a new era of excellence in Singapore
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.
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-đ¸ Secretion Profiling
2024
SMARTÂ CAMPÂ Authors
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
2024
SMARTÂ CAMPÂ Authors
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
2024
SMARTÂ CAMPÂ Authors
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`
2022
SMARTÂ CAMPÂ Authors
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
2022
SMARTÂ CAMPÂ Authors
Kerwin Kwek Zeming, Rohan Vernekar, Mui Teng Chua, Kai Yun Quek, Greg Sutton, Timm KrĂźger, Win Sen Kuan, Jongyoon Han
LabelâFree Biophysical Markers from Whole Blood Microfluidic Immune Profiling Reveal Severe Immune Response Signatures
2021
SMARTÂ CAMPÂ Authors
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
2021
SMARTÂ CAMPÂ Authors
Conference Presentations
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)
SMARTÂ CAMPÂ Authors
2024
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
SMARTÂ CAMPÂ Authors
2023
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
SMARTÂ CAMPÂ Authors
2023
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
SMARTÂ CAMPÂ Authors
2023
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
SMARTÂ CAMPÂ Authors
2023
Kerwin Kwek Zeming, Kai Yun Quek, Wei-Xiang Sin, Ka-Wai Cheung, Michael E. Birnbaum, Jongyoon Han
SMARTÂ CAMPÂ Authors
2023
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)
SMARTÂ CAMPÂ Authors
2022
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)
SMARTÂ CAMPÂ Authors
2022
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)
SMARTÂ CAMPÂ Authors
2022
Kevin S. Lee (Erbi Biosystems Inc.), Wei-Xiang Sin (SMART), Michael Birnbaum (MIT)
SMARTÂ CAMPÂ Authors
2022
Wei-Xiang Sin (SMART), Kevin S. Lee (Erbi Biosystems Inc.), Harry Lee (Erbi Biosystems Inc.), Michael Birnbaum (MIT)
SMARTÂ CAMPÂ Authors
2022
Kevin S. Lee (Erbi Biosystems Inc, Wei-Xiang Sin (SMART), Harry Lee (Erbi Biosystems Inc.), Michael Birnbaum (MIT)
SMARTÂ CAMPÂ Authors
2022
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.
