Extended Data Fig. 3: Small circRNA-SIINFEKL elicited potent T-cell responses in young adult mice. | Nature Biomedical Engineering

Extended Data Fig. 3: Small circRNA-SIINFEKL elicited potent T-cell responses in young adult mice.

From: Small circular RNAs as vaccines for cancer immunotherapy

Extended Data Fig. 3

a, Study design. C57BL/6 mice (n = 5) were vaccinated on day 0 and day 14, and PBMC T cell responses were analyzed starting from day 21. b, Tetramer staining on day21 – day70 showed that circRNA-SIINFEKL elicited potent SIINFEKL-specific CD8+ T cell response in mice (n = 5) that outperformed current benchmarks 5moU-modified CleanCap mRNA-OVA and CpG-adjuvanted OVA. c, circRNA-SIINFEKL elicited SIINFEKL-specific T cell memory (day 70). Tem: effector memory T cell; Tcm: central memory T cell. d, circRNA-SIINFEKL upregulated PD-1 expression on SIINFEKL-specific CD8+ T cells on day21. e, PD-1 MFI on live PBMC CD8+ T cells. f, circRNA-SIINFEKL enhanced PD-1 expression levels (MFI) and frequencies on SIINFEKL+CD8+ T cells than that on total CD8+ T cells in peripheral blood on day 21, indicating immune exhaustion often resulting from chronic immunostimulation and providing an opportunity to combine circRNA vaccines with immune checkpoint blockade for optimal T cell responses (Two-tailed paired t test). g, circRNA-SIINFEKL enabled mice to resist 3×105 EG7.OVA tumour challenge 70 days post-vaccination. Vaccine delivery by liposome, s.c. injected at tail base, 5 μg RNA, 2 nmole CpG, 20 μg OVA. *: relative to circRNA. h, Mouse body weights after tumour challenge. Data represent mean ± SD (b-e) and mean ± s.e.m. in other figure panels (n = 5). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, by one-way ANOVA with Bonferroni post-test unless denoted otherwise.

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