학술논문
PEGylated IL-10 (Pegilodecakin) Induces Systemic Immune Activation, CD8+ T Cell Invigoration and Polyclonal T Cell Expansion in Cancer Patients
Document Type
article
Author
Naing, Aung; Infante, Jeffrey R; Papadopoulos, Kyriakos P; Chan, Ivan H; Shen, Cong; Ratti, Navneet P; Rojo, Bianca; Autio, Karen A; Wong, Deborah J; Patel, Manish R; Ott, Patrick A; Falchook, Gerald S; Pant, Shubham; Hung, Annie; Pekarek, Kara L; Wu, Victoria; Adamow, Matthew; McCauley, Scott; Mumm, John B; Wong, Phillip; Van Vlasselaer, Peter; Leveque, Joseph; Tannir, Nizar M; Oft, Martin
Source
Cancer Cell. 34(5)
Subject
Language
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.