Fig. 6.
Effective immune adjuvant therapy reduces the threshold of neoantigen frequency required to obtain tumor regression benefit, Effect of mutation and immune intervention on orthotopic pancreatic tumor growth via bioluminescence imaging (n = 4–10). Mice were imaged and tumor signals were quantified on Day 10 post tumor inoculation, KPCF1 is a KPC cell line with KRASG12D mutation, 3F11 is a KPC cell line with KRASG12D/D153S mutation. Animals received either phosphate buffered saline (denoted as PBS), 50 μg of IL-12 plasmid DNA (denoted as IL12), or 50 μg of IL-10 trap plasmid DNA (denoted as IL-10 t), administered via lipid-protamine-DNA (LPD) nanoparticles intravenously on Day 7 and 9 post orthotopic tumor cell inoculation. The log normalized bioluminescence signal representing tumor burden was plotted on y-axis, and the percentage of cells with D153S mutation in the mixed inoculates were plotted on the x axis. Data fitted using third order polynomial (cubic) interpolation via GraphPad Prism 8.1.0. Horizontal line defines the threshold at which signal intensity for tumor burden reduces 1.5-logfold relative to untreated WT tumor. The numbers on the graph indicate the estimate of neoantigen carrying cells required to reduce the tumor burden by 32-fold or 1.5-logfold in terms of bioluminescence intensity- PBS (89%), IL-10 t (68%), and IL-12 (29%). Data show mean ± SEM.