Journal: Nature Cancer
Article Title: An oncolytic virus delivering tumor-irrelevant bystander T cell epitopes induces anti-tumor immunity and potentiates cancer immunotherapy
doi: 10.1038/s43018-024-00760-x
Figure Lengend Snippet: a , Schematic of the experimental design for b . Naive BALB/c mice were prime–boost immunized with SARS-CoV-2 RBD protein at an interval of 14 days and engrafted with 4T1 cells on day 60 after prime immunization. On days 7, 8, 9, 11 and 12 after tumor engraftment, recipients were intratumorally administered PBS, NDV-WT or NDV-RBD. Meanwhile, recipients of each group were administered anti-PD-L1 blocking antibody or control IgG antibody on days 10, 13 and 16 after tumor engraftment. b , c , Tumor growth curve ( b ) and Kaplan–Meier survival curve ( c ) from a . PBS and control ( n = 7 mice), PBS and anti-PD-L1 antibody ( n = 6 mice), NDV-WT and control ( n = 5 mice), NDV-WT and anti-PD-L1 antibody ( n = 6 mice), NDV-RBD and control ( n = 7 mice) and NDV-RBD and anti-PD-L1 antibody ( n = 7 mice) in b . PBS and control ( n = 6 mice), PBS and anti-PD-L1 antibody ( n = 4 mice), NDV-WT and control ( n = 6 mice), NDV-WT and anti-PD-L1 antibody ( n = 6 mice), NDV-RBD and control ( n = 8 mice) and NDV-RBD and anti-PD-L1 antibody ( n = 9 mice) in c . d , Flow cytometry analysis of CD8 + (top) and CD4 + (bottom) T cells from the PBMCs of SARS-CoV-2-uninfected donors and convalescent donor with COVID-19. Numbers adjacent to the outlined areas indicate percentages of SARS-CoV-2 RBD-stimulated IFN-γ + cells of CD8 + T cells or IFN-γ + cells of CD4 + T cells. e , Schematic experimental design for f . NCG mice were engrafted with PBMCs from HLA-A2-positive convalescent patients with COVID-19. After reconstruction of human T cells, these humanized NCG mice were engrafted with A375 cells and then intratumorally administered NDV-WT or NDV-RBD on days 7, 8, 9, 11 and 12 after tumor engraftment. f , Tumor growth curve of A375 tumor-bearing humanized NCG mice intratumorally treated with NDV-WT ( n = 5 mice) or NDV-RBD ( n = 4 mice) as indicated in e . g , Schematic experimental design for h . NCG mice were engrafted with PBMCs from HLA-A2-positive convalescent patients with COVID-19. Next, these reconstructed humanized NCG mice were engrafted with A375 cells and then intratumorally administered Ad5-WT or Ad5-RBD on days 7, 8, 9, 11 and 12 after tumor engraftment. h , Tumor growth curve of A375 tumor-bearing humanized NCG mice intratumorally treated with Ad5-WT ( n = 6 mice) or Ad5-RBD ( n = 6 mice) as indicated in g . Data ( b – d , f , h ) are representative of two independent experiments. Two-way ANOVA was used to compare tumor growth curves in b , f , h . The log-rank (Mantel–Cox) test was performed to compare survival curves among groups in c . Center values and error bars ( b , f , h ) indicate mean and s.e.m.
Article Snippet: To establish SARS-CoV-2-specific T cell memory, naive BALB/c mice were intranasally immunized with two doses of 10 μg SARS-CoV-2 RBD protein–mFC tag (Sino Biological, 40592-V05H) conjugated to 10 μg CpG ODN 1826 (Invitrogen, tlrl-1826) at an interval of 14 d.
Techniques: Blocking Assay, Control, Flow Cytometry