1. PEGylated IL-10 (Pegilodecakin) Induces Systemic Immune Activation, CD8+ T Cell Invigoration and Polyclonal T Cell Expansion in Cancer Patients
- Author
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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, and Oft, Martin
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Cancer ,Animals ,Antineoplastic Agents ,CD8-Positive T-Lymphocytes ,Cell Proliferation ,Cells ,Cultured ,Granzymes ,Humans ,Immunotherapy ,Interferon-gamma ,Interleukin-10 ,Interleukin-18 ,Lymphocyte Activation ,Lymphocytes ,Tumor-Infiltrating ,Mice ,Mice ,Inbred C57BL ,Neoplasms ,Polyethylene Glycols ,Programmed Cell Death 1 Receptor ,AM0010 ,CD8(+) T cell ,IL-10 ,PEGylated Interleukin 10 ,T cell invigoration ,Th1 ,clinical trial ,clonal expansion ,clonality ,pegilodecakin ,Neurosciences ,Oncology & Carcinogenesis ,Biochemistry and cell biology ,Oncology and carcinogenesis - 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.
- Published
- 2018