PEGylated IL-10 (Pegilodecakin) Induces Systemic Immune Activation, CD8+ T Cell Invigoration and Polyclonal T Cell Expansion in Cancer Patients

Cancer Cell. 2018 Nov 12;34(5):775-791.e3. doi: 10.1016/j.ccell.2018.10.007.


Tumor-reactive T cell exhaustion prevents the success of immune therapies. Pegilodecakin activates intratumoral CD8+ T cells in mice and induces objective tumor responses in patients. Here we report that pegilodecakin induces hallmarks of CD8+ T cell immunity in cancer patients, including elevation of interferon-γ and GranzymeB, expansion and activation of intratumoral CD8+ T cells, and proliferation and expansion of LAG-3+ PD-1+ CD8+ T cells. On pegilodecakin, newly expanded T cell clones, undetectable at baseline, become 1%-10% of the total T cell repertoire in the blood. Elevation of interleukin-18, expansion of LAG-3+ PD-1+ T cells and novel T cell clones each correlated with objective tumor responses. Combined pegilodecakin with anti-PD-1 increased the expansion of LAG-3+ PD-1+ CD8+ T cells.

Keywords: AM0010; CD8(+) T cell; IL-10; PEGylated Interleukin 10; T cell invigoration; Th1; clinical trial; clonal expansion; clonality; pegilodecakin.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Granzymes / blood
  • Humans
  • Immunotherapy / methods*
  • Interferon-gamma / blood
  • Interleukin-10 / chemistry
  • Interleukin-10 / pharmacology*
  • Interleukin-10 / therapeutic use
  • Interleukin-18 / metabolism
  • Lymphocyte Activation / drug effects*
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • Polyethylene Glycols / therapeutic use*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors


  • Antineoplastic Agents
  • IFNG protein, human
  • IL10 protein, human
  • Interleukin-18
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • pegilodecakin
  • Interleukin-10
  • Polyethylene Glycols
  • Interferon-gamma
  • GZMB protein, human
  • Granzymes