Fig. 8: Monovalent or multivalent small circRNA vaccines for robust combination immunotherapy of multiple types of tumour.
From: Small circular RNAs as vaccines for cancer immunotherapy
a, Design of tumour immunotherapy studies in mice. Tumour cells were inoculated subcutaneously in mouse flank, and treatment started when tumour volumes were around 50 mm3. Vaccines were loaded in LNPs and subcutaneously injected at tail base; antibodies were intraperitoneally injected. b, Average TC-1 tumour volumes after treatment with circRNA-E743–62 + anti-PD-1 and controls (n = 6–7). c, Spider plots of individual TC-1 tumour growth curves and complete regression (CR) rates after the above treatment. In b and c, vaccine, 5 μg RNA, 5 μg CpG, 10 μg E743–62 peptide antigens; anti-PD-1, 200 μg. Asterisks: statistical significance relative to circRNA + ICB. d, Average volumes of B16F10 melanoma treated with MHC-I/II-restricted tetravalent circRNA-T2/g/T1/T1 vaccine, alone or combined with anti-PD-1 + anti-CTLA-4. Asterisks denote statistical significance relative to circRNA-T2/g/T1/T1. e, B16F10 melanoma tumour growth after circRNA-T2/g/T1/T1 vaccine treatment and lymphocyte depletion. Asterisks: statistical significance relative to circRNA-T2/g/T1/T1. f, Spider plots of individual B16F10 melanoma tumour growth curves and CR rates. g, Kaplan–Meier survival curves of the as-treated B16F10 melanoma-bearing mice. Asterisks: statistical significance relative to circRNA + ICB. In d–g, circRNA, 10 μg; antibodies, 100 μg per ICB antibody, 200 μg anti-CD8, anti-CD4 or anti-NK1.1. h, Average (left) and individual (right) tumour growth curves of BrafV600E SM1 melanoma treated with circRNA-T2/g/T1/T1 combined with anti-PD-1 + anti-CTLA-4, as well as controls. Asterisks: statistical significance relative to circRNA-T2/g/T1/T1. i, Kaplan–Meier survival curves of BrafV600E SM1 melanoma-bearing mice treated as above. Asterisks: statistical significance relative to circRNA + ICB. In h and i, circRNA, 30 μg; ICB antibodies, 200 μg each. Vaccines: loaded in SM-102 LNPs and subcutaneously injected at mouse tail base. Data represent mean ± s.e.m. (n = 6–8). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, by one-way ANOVA with Bonferroni post-test unless denoted otherwise.
