Fig. 1: RCT-aAPCs and mRBC-aAPCs promote antigen-specific T-cell expansion, memory formation, and cytotoxicity towards tumor cells in vitro and in vivo. | Nature Communications

Fig. 1: RCT-aAPCs and mRBC-aAPCs promote antigen-specific T-cell expansion, memory formation, and cytotoxicity towards tumor cells in vitro and in vivo.

From: Engineered red blood cells as an off-the-shelf allogeneic anti-tumor therapeutic

Fig. 1

a EG7.OVA percent killing by RCT-activated OT-1 cells (n = 3). b CD45.1 Pep Boy mice were randomized (~180 mm3; n = 5), treated with naïve OT-1 cells, and dosed with 1 × 109 mRBC-CTRL or mRBC-aAPC. c OT-1 number on days 0, 3, and 6. One-way ANOVA compared to mRBC-CTRL; Day 3: mRBC-OVA-4-1BBL-IL-15 P < 0.0001; Day 6: mRBC-OVA-4-1BBL-IL-15 P < 0.0001, mRBC-OVA-4-1BBL-IL-12 P = 0.0001. d Memory OT-1 number on day 6 in blood. One-way ANOVA compared to mRBC-CTRL; Tscm (stem memory T cells): mRBC-OVA-4-1BBL P = 0.038; Tcm: mRBC-OVA-4-1BBL P = 0.0016, mRBC-OVA-4-1BBL-IL-15 P = 0.025; Tem: mRBC-OVA-4-1BBL-IL-15 P = 0.0001, mRBC-OVA-4-1BBL-IL-15 P < 0.0001. e CD45.1 Pep Boy mice were randomized (~150 mm3; n = 8), treated with naïve OT-1 cells, and dosed with 2.5 × 108 mRBC-CTRL or mRBC-aAPC. f Tumor growth and g survival. Log-rank (Mantel-Cox, one-sided) test of survival curve; mRBC-OVA-4-1BBL vs mRBC-OVA-4-1BBL-IL-12 and PBS vs mRBC-OVA-4-1BBL-IL-12 P < 0.0001. h CD45.1 Pep Boy mice were randomized (~230 mm3; n = 8), treated with naïve OT-1 cells, and dosed with OVA241-270 peptide with IFA or 1 × 109 mRBC-CTRL, mRBC-4-1BBL-IL-12, or mRBC-OVA-4-1BBL-IL-12. i Tumor growth. j OT-1 number in blood on Day 6. One-way ANOVA compared to mRBC-CTRL; mRBC-OVA-4-1BBL-IL-12 P < 0.0001. k CD45.1 Pep Boy mice were randomized (~175 mm3; n = 5), treated with naïve OT-1 cells, and dosed with 1 × 109 mRBC-CTRL or a dose titration of mRBC-OVA-4-1BBL-IL-12 (1 × 109, 2.5 × 108). l OT-1 numbers in 50 μL blood and per gram of tumor on day 7. One-way ANOVA compared to mRBC-CTRL; blood: 1 × 109P < 0.0001; tumor: 1 × 109 P = 0.0046. m TCRβ sequencing analyses of OT-1 TCR frequency in blood on day 0 (pre-blood), on day 7 (post-blood), and in tumor on day 7. One-way ANOVA compared to mRBC-CTRL; post blood: 1 × 109 P < 0.0001; tumor: 3 × 108 P = 0.02, 1 × 109 P < 0.0001. n Polyfunctionality (granzyme B+IFNγ+ %) in the tumor-infiltrating OT-1 cells on day 7. One-way ANOVA compared to mRBC-CTRL; 1 × 109 P = 0.0021. Data are depicted as mean ± s.d. and are representative of four (l blood), two (a, c, d, f, g, l tumor, n), or one (i, j, m) independent experiments. Source data are provided as a Source Data file.

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