Cancer Cell
Volume 34, Issue 5, 12 November 2018, Pages 775-791.e3
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Article
PEGylated IL-10 (Pegilodecakin) Induces Systemic Immune Activation, CD8+ T Cell Invigoration and Polyclonal T Cell Expansion in Cancer Patients

https://doi.org/10.1016/j.ccell.2018.10.007Get rights and content
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Highlights

  • Pegilodecakin induces systemic and intratumoral CD8+ T cell activation in patients

  • PD-1+ Lag3+ CD8+ T cells and previously undetected T cell clones are expanded

  • IFN-γ, IL-18, GranzymeB, and FasL are elevated across tumor types

  • The magnitude of systemic immune activation correlates with tumor response

Summary

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

PEGylated Interleukin 10
IL-10
pegilodecakin
AM0010
clinical trial
CD8+ T cell
clonality
clonal expansion
T cell invigoration
Th1

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11

These authors contributed equally

12

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