NIH Research Festival
NHS-IL12 (now designated PDS0301) is a tumor-targeting immunocytokine targeting DNA/histones in necrotic areas of the tumor microenvironment. NHS-IL12 has shown promising results in preclinical studies as a monotherapy and in combination with other anti-cancer therapies such as the HDAC inhibitor Entinostat. The first-in-human clinical trial (NCT01417546) administered NHS-IL12 subcutaneously every four weeks (Q4W) and was expanded to include cohorts with bi-weekly treatment (Q2W). Here, we present immune correlates in peripheral blood to determine the impact of the dose level and schedule of NHS-IL12 on immune activation and evaluate immune correlates of clinical response.
Serum was evaluated for levels of cytokines/soluble factors by Elisa and Mesoscale assays, and peripheral blood mononuclear cells were assessed for 158 immune cell subsets by multicolor flow cytometry. New assays to detect soluble NK ligands and more extensively characterize the association between NK lysis and phenotype were developed in healthy donor samples.
Patients treated in the Q2W cohort with a dose of 16.8 mcg/kg NHS-IL12 (versus those with 12.0 mcg/kg) exhibited greater increases in serum IFNŒ≥, TNFŒ±, and sPD-1, and greater increases in peripheral ki67+ mature NK, CD8+ T, and NKT cells. Greater immune activation was also seen in the Q2W versus Q4W cohort. Lower baseline levels of monocytes and plasmacytoid dendritic cells and greater increases after treatment in NK and CD8+ T cell subsets associated with improved clinical outcome.
These findings demonstrate enhanced immune activation of both NK and T cells with higher dose levels and more frequent dosing of NHS-IL12.
Scientific Focus Area: Immunology
This page was last updated on Monday, September 25, 2023