IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor

Nat Biotechnol. 2018 Apr;36(4):346-351. doi: 10.1038/nbt.4086. Epub 2018 Mar 5.


Infiltration, accumulation, and survival of chimeric antigen receptor T (CAR-T) cells in solid tumors is crucial for tumor clearance. We engineered CAR-T cells to express interleukin (IL)-7 and CCL19 (7 × 19 CAR-T cells), as these factors are essential for the maintenance of T-cell zones in lymphoid organs. In mice, 7 × 19 CAR-T cells achieved complete regression of pre-established solid tumors and prolonged mouse survival, with superior anti-tumor activity compared to conventional CAR-T cells. Histopathological analyses showed increased infiltration of dendritic cells (DC) and T cells into tumor tissues following 7 × 19 CAR-T cell therapy. Depletion of recipient T cells before 7 × 19 CAR-T cell administration dampened the therapeutic effects of 7 × 19 CAR-T cell treatment, suggesting that CAR-T cells and recipient immune cells collaborated to exert anti-tumor activity. Following treatment of mice with 7 × 19 CAR-T cells, both recipient conventional T cells and administered CAR-T cells generated memory responses against tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allografts
  • Animals
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell- and Tissue-Based Therapy*
  • Chemokine CCL19 / administration & dosage*
  • Chemokine CCL19 / genetics
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation
  • Gene Expression Regulation / drug effects
  • Interleukin-7 / administration & dosage*
  • Interleukin-7 / genetics
  • Mice
  • Receptors, Antigen, T-Cell / administration & dosage*
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Chimeric Antigen / administration & dosage*
  • Receptors, Chimeric Antigen / immunology


  • Ccl19 protein, mouse
  • Chemokine CCL19
  • Interleukin-7
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen