Mode of Action

IL-7 does not only increase the number of naïve and memory T cells but also enhances T cell functionality. For instance, IL-7 broadens T cell receptor (TCR) diversity, and consequentially prepares T cells to respond to even subdominant epitopes. Also, IL-7 enhances T cell homing and infiltration to tumor by increasing homing chemokine activity and antagonizing various inhibitory networks. IL-7’s action of increase in the number of tumor reactive T cells including memory phenotype cells and decrease in immunosuppression would induce persistent and long-lasting anti-tumor T cell response. (Michel Morre, Stéphanie Beq, Targ Oncol (2012) 7:55-68; Beq S et al. Blood (2009) 114(4):816–825; Li B et al. Clin Immunol (2007) 123(2):155–165; Pellegrini M et al. Nat Med (2009) 15(5):528–536)

Besides the known mechanism of NT-I7, a few recent publications suggested good scientific rationales how NT-I7 could make a synergetic combination with an immune checkpoint inhibitor. One publication implies the IL-7 signaling is critical to show the efficacy of checkpoint inhibitors, and suggests that a potential combination of immune checkpoint therapy and IL-7 signaling would boost efficacy. (Published by MD Anderson Aug 2016: Nature Communications 7, Article number: 12335 (2016) doi:10.1038/ncomms12335) Another recent publication demonstrated that long-acting IL-7 and anti-PD-L1 combo therapy exhibited more viral-specific CD8 T cells and improved coproduction of CD8 T cells secreting IFN-g and TNF-a, as anti-PD-L1 treatment induces an increase of IL-7R(CD127). (Science, 2016, 354, 1160)

IL-7 signaling is essential for the effect of immune checkpoint combo therapy

Nature Communications 7, Article number: 12335
(2016) doi:10.1038/ncomms12335

  • Combo treatment to IL-7R -/- mice bearing tumor resulted in low survival.
  • In sub-lethally irradiated mice followed by tumor inoculation and adoptive T cell transfer with wild type or IFN-g R-/-or IL-7R -/ T cells, combination IC therapy shows no benefit with transfer of IL-7R -/ T cells

In chronic infection model, IL-7 & anti-PD-L1 combo therapy exhibited more viral-specific P14+ CD8 T cells

Science, 2016, 354, 1160

  • Anti-PD-L1 treatment induce increase of IL-7R (CD127), but not IL-15R (CD122).
  • Long acting IL-7 (IL-7 i.c. = IL-7/mAb immune complex) + anti-PD-L1 resulted in more viral-specific (P14+) CD8 T cells.
  • Long acting IL-7 + anti-PD-L1 improved coproduction of CD8 T cells secreting IFN-g and TNF-a