Clinically relevant T cell expansion media activate distinct metabolic programs uncoupled from cellular function

Sarah MacPherson, Sarah Keyes, Marisa K. Kilgour, Julian Smazynski, Vanessa Chan, Jessica Sudderth, Tim Turcotte, Adria Devlieger, Jessie Yu, Kimberly S. Huggler, Jason R. Cantor, Ralph J. DeBerardinis, Christopher Siatskas, Julian J. Lum

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)380-393
Number of pages14
JournalMolecular Therapy - Methods and Clinical Development
Volume24
DOIs
StatePublished - Mar 10 2022

Keywords

  • C tracer analysis
  • T cell expansion
  • cell-based immunotherapy
  • culture media
  • metabolism
  • phenotype

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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