Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock


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


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 IFNgamma, TNFalpha, 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.

Authors: Toney NJ, Gatti-Mays ME, Tschernia NP, Strauss J, Gulley JL, Schlom J, Donahue RN.
Journal: Int Immunopharmacol . 2023 Mar;116:109736. doi: 10.1016/j.intimp.2023.109736.
Year: 2023
PubMed: PMID: 37234190 (Go to PubMed)