Fig. 5
From: Lipid nanoparticles deliver DNA-encoded biologics and induce potent protective immunity
Therapeutic effects of LNP-M/DNA against PD-L1, p53R172H, PD1, or p53R282W in several syngeneic tumor models. A-C LNP-M/DNA expressing PD-L1 elicits anti-PD-L1 antibodies and anti-tumor activities. BALB/c mice (n = 5 per group) were immunized with three doses of LNP-M/DNA expressing mouse PD-L1 at days 7, 17, and 24. A20 tumor cells were inoculated on day 0. The first twos doses were delivered intramuscularly and the last dose intratumorally. Two weeks after the last dose, sera were taken to measure the titers of anti-PD-L1 IgG antibodies (A), and tumor volumes (B) and inhibition (C) were assessed. D-F LNP-M/DNA expressing p53-R172H elicits anti-p53 antibodies and anti-tumor activities. 129 Sv/E mice (n = 5 per group) were immunized with three doses of LNP-M/DNA expressing mouse p53-R172H at days 7, 17, and 24. 344SQ tumor cells were inoculated on day 0. The first two doses were delivered intramuscularly and the last dose intratumorally. Two weeks after the last dose, sera were taken to measure the titers of anti-p53R172H IgG antibodies (D), and tumor volumes (E) and inhibition (F) were assessed. G-I LNP-M/DNA expressing the antibody against mouse PD1 elicits anti-tumor activities. MC38 tumor cells were inoculated into C57BL/6J mice, and LNP-M/pPD1-mAb was injected intratumorally on days 14 and 21 post-tumor inoculation (n = 5 mice per group). Five days after the first dose, the expression of PD1 on CD8+ T cells from the tumors was detected using FACS. Tumor volumes (H) and inhibition (I) were assessed. J-N LNP-M/DNA expressing the antibody against human p53R282W elicited anti-tumor activities in MC38 syngeneic models. MC38-p53KO/R282W cells were injected subcutaneously into mice and given intratumoral injections of LNP-M/pR282W-mAb on days 14 and 21 post-tumor inoculation (n = 5 mice per group). The percentages of Cd45+ and human Fc+ cells within tumors were determined using FACS (J). Tumor volumes were measured (K), and tumor inhibition was calculated (L). In the metastatic model, MC38-p53KO/R282W cells were inoculated intravenously (n = 10 mice per group), and mice were treated with LNP-M/pR282W-mAb; representative images of metastatic nodules on the lung surface and animal survival were shown in (M). MC38-p53KO/R282W cells were inoculated intraperitoneally before treatment (n = 10 mice per group). Representative images of rectal MC38-p53KO/R282W tumors and animal survival were shown in (N). O-Q LNP-M/pR282W-mAb inhibits HupT3 tumors. NSG mice were inoculated with HupT3 cells with an endogenous p53 R282W mutation on day 0, given PBMCs (1 × 107/mouse) intravenously on day 10, and treated by LNP-M/pR282W-mAb on days 14, 19, and 24 (n = 5 mice). FACS detected the percentage of human CD56+ NK cells in TILs (O), tumor volumes were measured (P), and tumor inhibition rates were calculated (Q). Data were presented as mean ± SD. Statistical significance was set at **p < 0.01, ***p < 0.001 and ****p < 0.0001; ns, not significant