Immune correlates with response in patients with metastatic solid tumors treated with a tumor targeting immunocytokine NHS-IL12.

Autor: Toney NJ; Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Gatti-Mays ME; The Pelotonia Institute for Immuno-Oncology, Division of Medical Oncology, The Ohio State University, Columbus OH, USA., Tschernia NP; Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Strauss J; Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Gulley JL; Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Schlom J; Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Donahue RN; Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2023 Mar; Vol. 116. Date of Electronic Publication: 2023 Feb 16.
DOI: 10.1016/j.intimp.2023.109736
Abstrakt: The immunocytokine NHS-IL12 delivers IL-12 to the tumor microenvironment by targeting DNA/histones in necrotic areas. The first-in-human clinical trial administered NHS-IL12 subcutaneously in 59 patients treated every four weeks (Q4W), with a maximum tolerated dose of 16.8 mcg/kg. The phase I study was expanded to include a high-exposure cohort that received bi-weekly treatment (Q2W) with two dose levels of NHS-IL12: 12.0 mcg/kg and 16.8 mcg/kg. Here, patients given NHS-IL12 were analyzed both prior to and early after treatment for effects on 10 serum soluble analytes, complete blood counts, and 158 peripheral immune subsets. Higher levels of immune activation were seen with a dose of 16.8 mcg/kg versus 12.0 mcg/kg in patients in the high-exposure cohort, as evidenced by greater increases in serum IFNγ, TNFα, and soluble PD-1, and greater increases in frequencies of peripheral ki67 + mature natural killer (NK), CD8 + T, and NKT cells. Greater immune activation was also seen in the Q2W versus Q4W cohort, as demonstrated by greater increases in pro-inflammatory serum analytes, ki67 + CD8 + T, NK, and NKT cells, intermediate monocytes, and a greater decrease in CD73 + T cells. Specific immune analytes at baseline including lower levels of monocytes and plasmacytoid dendritic cells, and early changes after treatment such as an increase in refined NK cell subsets and total CD8+ T cells, associated with better clinical response. These findings may help to guide future schedule and dosing regimens of clinical studies of NHS-IL12 as monotherapy and in combination therapies.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Databáze: MEDLINE
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