Naing A, Infante JR, Papadopoulos KP, Chan IH, Shen C, Ratti NP, Rojo B, Autio KA, Wong DJ, Patel MR, Ott PA, Falchook GS, Pant S, Hung A, Pekarek KL, Wu V, Adamow M, McCauley S, Mumm JB, Wong P, Van Vlasselaer P, Leveque J, Tannir NM and Oft M.

Cancer Cell. 2018 Nov 12;34(5):775-791.e3

DOI: 10.1016/j.ccell.2018.10.007

Abstract

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.