Augmentation of Antitumor Immunity by Human and Mouse CAR T Cells Secreting IL-18

Cell Rep. 2017 Sep 26;20(13):3025-3033. doi: 10.1016/j.celrep.2017.09.002.


The effects of transgenically encoded human and mouse IL-18 on T cell proliferation and its application in boosting chimeric antigen receptor (CAR) T cells are presented. Robust enhancement of proliferation of IL-18-secreting human T cells occurred in a xenograft model, and this was dependent on TCR and IL-18R signaling. IL-18 augmented IFN-γ secretion and proliferation of T cells activated by the endogenous TCR. TCR-deficient, human IL-18-expressing CD19 CAR T cells exhibited enhanced proliferation and antitumor activity in the xenograft model. Antigen-propelled activation of cytokine helper ensemble (APACHE) CAR T cells displayed inducible expression of IL-18 and enhanced antitumor immunity. In an intact mouse tumor model, CD19-IL-18 CAR T cells induced deeper B cell aplasia, significantly enhanced CAR T cell proliferation, and effectively augmented antitumor effects in mice with B16F10 melanoma. These findings point to a strategy to develop universal CAR T cells for patients with solid tumors.

Keywords: IL-18; T cell; adoptive transfer; cancer; chimeric antigen receptor; immunotherapy.

MeSH terms

  • Animals
  • Cell Proliferation
  • Humans
  • Interleukin-18 / metabolism*
  • Mice
  • Receptors, Antigen, T-Cell / metabolism*


  • IL18 protein, human
  • Interleukin-18
  • Receptors, Antigen, T-Cell