TY - JOUR
T1 - Clinically relevant T cell expansion media activate distinct metabolic programs uncoupled from cellular function
AU - MacPherson, Sarah
AU - Keyes, Sarah
AU - Kilgour, Marisa K.
AU - Smazynski, Julian
AU - Chan, Vanessa
AU - Sudderth, Jessica
AU - Turcotte, Tim
AU - Devlieger, Adria
AU - Yu, Jessie
AU - Huggler, Kimberly S.
AU - Cantor, Jason R.
AU - DeBerardinis, Ralph J.
AU - Siatskas, Christopher
AU - Lum, Julian J.
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/3/10
Y1 - 2022/3/10
N2 - Ex vivo expansion conditions used to generate T cells for immunotherapy are thought to adopt metabolic phenotypes that impede therapeutic efficacy in vivo. The comparison of five different culture media used for clinical T cell expansion revealed unique optima based on different output variables, including proliferation, differentiation, function, activation, and mitochondrial phenotypes. The extent of proliferation and function depended on the culture media rather than stimulation conditions. Moreover, the expanded T cell end products adapted their metabolism when switched to a different media formulation, as shown by glucose and glutamine uptake and patterns of glucose isotope labeling. However, adoption of these metabolic phenotypes was uncoupled to T cell function. Expanded T cell products cultured in ascites from ovarian cancer patients displayed suppressed mitochondrial activity and function irrespective of the ex vivo expansion media. Thus, ex vivo T cell expansion media have profound impacts on metabolism and function.
AB - Ex vivo expansion conditions used to generate T cells for immunotherapy are thought to adopt metabolic phenotypes that impede therapeutic efficacy in vivo. The comparison of five different culture media used for clinical T cell expansion revealed unique optima based on different output variables, including proliferation, differentiation, function, activation, and mitochondrial phenotypes. The extent of proliferation and function depended on the culture media rather than stimulation conditions. Moreover, the expanded T cell end products adapted their metabolism when switched to a different media formulation, as shown by glucose and glutamine uptake and patterns of glucose isotope labeling. However, adoption of these metabolic phenotypes was uncoupled to T cell function. Expanded T cell products cultured in ascites from ovarian cancer patients displayed suppressed mitochondrial activity and function irrespective of the ex vivo expansion media. Thus, ex vivo T cell expansion media have profound impacts on metabolism and function.
KW - C tracer analysis
KW - T cell expansion
KW - cell-based immunotherapy
KW - culture media
KW - metabolism
KW - phenotype
UR - http://www.scopus.com/inward/record.url?scp=85125530440&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85125530440&partnerID=8YFLogxK
U2 - 10.1016/j.omtm.2022.02.004
DO - 10.1016/j.omtm.2022.02.004
M3 - Article
C2 - 35284590
AN - SCOPUS:85125530440
SN - 2329-0501
VL - 24
SP - 380
EP - 393
JO - Molecular Therapy Methods and Clinical Development
JF - Molecular Therapy Methods and Clinical Development
ER -