TY - JOUR
T1 - Efficient recovery of potent tumour-infiltrating lymphocytes through quantitative immunomagnetic cell sorting
AU - Wang, Zongjie
AU - Ahmed, Sharif
AU - Labib, Mahmoud
AU - Wang, Hansen
AU - Hu, Xiyue
AU - Wei, Jiarun
AU - Yao, Yuxi
AU - Moffat, Jason
AU - Sargent, Edward H.
AU - Kelley, Shana O.
N1 - Funding Information:
S.O.K., Z.W. and S.A. have a filed patent application (number 63/183,350) using parts of the data reported in this article. S.O.K. has a patent titled ‘Device for capture of particles in a flow’ (US10073079) licensed to Cellular Analytics. S.O.K. received research funds from Amgen through a sponsored research agreement. J.M. is a shareholder of Century Therapeutics and Aelian Biotechnology.
Funding Information:
We thank J. Charron and N. Simard at the Temerty Faculty of Medicine, University of Toronto for help in FACS sorting; T. Chen at the Sick Children Hospital, Toronto for help in tumour dissociation; M. Peralta at the University Health Network (UHN) for help in immunohistochemistry; W. Xiao at UHN for help in intravascular injection; J. Henderson at the Faculty of Pharmacy, University of Toronto; J. Cathcart and J. Jonkman at UHN for help in image quantitation; and anonymous technician(s) at Miltenyi Biotec for information regarding the MACSQuant Tyto system. This research was supported in part by the Canadian Institutes of Health Research (grant no. FDN-148415) and the Collaborative Health Research Projects program (CIHR/NSERC partnered). This research is part of the University of Toronto?s Medicine by Design initiative, which receives funding from the Canada First Research Excellence Fund. Z.W. was supported by an Alexander Graham Bell Canada Graduate Scholarship and a Centre for Pharmaceutical Oncology Graduate Student Scholarship.
Funding Information:
We thank J. Charron and N. Simard at the Temerty Faculty of Medicine, University of Toronto for help in FACS sorting; T. Chen at the Sick Children Hospital, Toronto for help in tumour dissociation; M. Peralta at the University Health Network (UHN) for help in immunohistochemistry; W. Xiao at UHN for help in intravascular injection; J. Henderson at the Faculty of Pharmacy, University of Toronto; J. Cathcart and J. Jonkman at UHN for help in image quantitation; and anonymous technician(s) at Miltenyi Biotec for information regarding the MACSQuant Tyto system. This research was supported in part by the Canadian Institutes of Health Research (grant no. FDN-148415) and the Collaborative Health Research Projects program (CIHR/NSERC partnered). This research is part of the University of Toronto’s Medicine by Design initiative, which receives funding from the Canada First Research Excellence Fund. Z.W. was supported by an Alexander Graham Bell Canada Graduate Scholarship and a Centre for Pharmaceutical Oncology Graduate Student Scholarship.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2022/2
Y1 - 2022/2
N2 - Adoptive cell therapies require the recovery and expansion of highly potent tumour-infiltrating lymphocytes (TILs). However, TILs in tumours are rare and difficult to isolate efficiently, which hinders the optimization of therapeutic potency and dose. Here we show that a configurable microfluidic device can efficiently recover potent TILs from solid tumours by leveraging specific expression levels of target cell-surface markers. The device, which is sandwiched by permanent magnets, balances magnetic forces and fluidic drag forces to sort cells labelled with magnetic nanoparticles conjugated with antibodies for the target markers. Compared with conventional cell sorting, immunomagnetic cell sorting recovered up to 30-fold higher numbers of TILs, and the higher levels and diversity of the recovered TILs accelerated TIL expansion and enhanced their therapeutic potency. Immunomagnetic cell sorting also allowed us to identify and isolate potent TIL subpopulations, in particular TILs with moderate levels of CD39 (a marker of T-cell reactivity to tumours and T-cell exhaustion), which we found are tumour-specific, self-renewable and essential for the long-term success of adoptive cell therapies.
AB - Adoptive cell therapies require the recovery and expansion of highly potent tumour-infiltrating lymphocytes (TILs). However, TILs in tumours are rare and difficult to isolate efficiently, which hinders the optimization of therapeutic potency and dose. Here we show that a configurable microfluidic device can efficiently recover potent TILs from solid tumours by leveraging specific expression levels of target cell-surface markers. The device, which is sandwiched by permanent magnets, balances magnetic forces and fluidic drag forces to sort cells labelled with magnetic nanoparticles conjugated with antibodies for the target markers. Compared with conventional cell sorting, immunomagnetic cell sorting recovered up to 30-fold higher numbers of TILs, and the higher levels and diversity of the recovered TILs accelerated TIL expansion and enhanced their therapeutic potency. Immunomagnetic cell sorting also allowed us to identify and isolate potent TIL subpopulations, in particular TILs with moderate levels of CD39 (a marker of T-cell reactivity to tumours and T-cell exhaustion), which we found are tumour-specific, self-renewable and essential for the long-term success of adoptive cell therapies.
UR - http://www.scopus.com/inward/record.url?scp=85123757434&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85123757434&partnerID=8YFLogxK
U2 - 10.1038/s41551-021-00820-y
DO - 10.1038/s41551-021-00820-y
M3 - Article
C2 - 35087171
AN - SCOPUS:85123757434
SN - 2157-846X
VL - 6
SP - 108
EP - 117
JO - Nature Biomedical Engineering
JF - Nature Biomedical Engineering
IS - 2
ER -
