Short-term culture with IL-2 is beneficial for potent memory chimeric antigen receptor T cell production

Biochem Biophys Res Commun. 2018 Jan 8;495(2):1833-1838. doi: 10.1016/j.bbrc.2017.12.041. Epub 2017 Dec 8.

Abstract

Interleukin-2 (IL-2) has been extensively used to boost the body's immune cells, especially T cells. IL-2 is a cytokine that for many years was used to activate and amplify T cells. Due to its potent T cell growth-inducing functions in vitro, for many years, IL-2 was used for the culture and expansion of various T cell products, including tumor-infiltrating lymphocytes (TIL), T cell receptors T cells (TCR T), or genetically engineered cells with chimeric antigen receptors T cells (CAR T). Despite its positive effect on T cell production, the side-effect is not well studied. Here, we reported that long-term culture with IL-2 promotes terminal differentiation and impairs rather than boosts the function of chimeric antigen receptor T cells. However, short-term culture with IL-2 predominantly generates memory CAR T cell favorable for cancer treatment.

Keywords: Chimeric antigen receptor; IL-2; Memory T cell.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Cell Culture Techniques / methods
  • Cell Differentiation
  • Cell Line, Tumor
  • Cells, Cultured
  • Humans
  • Immunologic Memory
  • Interleukin-2 / immunology
  • Interleukin-2 / pharmacology*
  • Mice
  • Neoplasms / immunology
  • Neoplasms / therapy
  • Precision Medicine
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction / immunology
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / immunology*
  • Xenograft Model Antitumor Assays

Substances

  • IL2 protein, human
  • Interleukin-2
  • Receptors, Antigen, T-Cell