Fig. 6.
A cytokine cocktail-modulated CD62Lhigh phenotype correlates with persistence and superior anti-tumor activities in murine models. a The enhanced engraftment in LN of NSG mice. After 30 days, LN from each mouse in 3 groups was analyzed by flow cytometry using anti-human CD3 antibody on left (upper panel); the total number of engrafted human T cells were calculated using Fluorospheres, and the average ± SD from 4 mice/group was calculated and plotted on right. M1–M4 on top of each image indicates mice on each individual group. Lower panel T cells before infusion were analyzed using a panel of antibodies; the histograms representing each marker were overlaid, and the lines represent each group of cells was indicated on left. b A cytokine cocktail-modulated CD62Lhigh phenotype of anti-tumor T cells conveys the superior anti-tumor activities in a murine IC tumor model. The therapeutic procedures were schematically illustrated. C57bl/6 mice were implanted with IC tumor using KR158 cells for 5 days before ACT, and 1 day before, ACT mice received 5 Gy total body irradiation. On day 0, 1 × 106 ex vivo-cultured T cells were infused IV followed by ttRNA–DC vaccination ID. After ACT, two additional ttRNA–DC vaccinations were executed on a weekly basis by IP injection. c A cytokine cocktail-modulated T cells lead to a prolonged survival. Mice (7 mice/group) were implanted with IC tumor, and the groups indicate the use of DC alone or combined with different types of T cells were shown on right; the cocktail T group represents T cells cultured with a cocktail in the absence of DC. For survival, log-rank test was performed. Asterisks indicate p < 0.001. d A cytokine cocktail directly modulates the phenotype of ex vivo ttRNA–DC-expanded anti-tumor T cells. The phenotype of ex vivo-cultured anti-tumor T cells was analyzed before infusion using a panel of antibodies; the percentage of CD8, CD62L, and CD44 was plotted from 4 independent experiments