Journal: Nature Medicine

Article Title: Immunogenicity and therapeutic targeting of a public neoantigen derived from mutated PIK3CA

doi: 10.1038/s41591-022-01786-3

Figure Lengend Snippet: a , Experimental overview for the evaluation of the in vivo anti-tumor efficacy and safety of targeting Mut PIK3CA using TCR-transduced CD8 + T cells. Mice were randomized between indicated treatment groups once subcutaneously (s.c.) implanted HCC70-Mut PIK3CA or HCC70-WT PIK3CA tumors were established to ~75 mm 3 . All mice received a twice-weekly intraperitoneal injection of 1 μg of IL-15 pre-complexed with IL-15Rα-Fc (1:1 M) and intravenous injection of CD8 + T cells transduced with TCR4, CD8 + T cells transduced with an influenza (Flu)-specific TCR, or PBS. Mice received 7.5 × 10 6 and 2.5 × 10 6 TCR + T cells on D0 and D3 after randomization. Tumor volumes ( b ) and overall survival ( c ) of mice bearing HCC70-Mut PIK3CA tumors infused with the indicated treatment. Tumor volumes ( d ) and overall survival ( e ) of mice bearing established HCC70-WT PIK3CA tumors infused with the indicated treatment. Data in b and d are shown as mean ± s.e.m. and are representative of two independently performed experiments (TCR4 n = 10, Flu TCR n = 5, PBS n = 5). *** P < 0.001 and NS using two-way ANOVA. Pooled survival data from two identically performed experiments are shown in c and e and are plotted as a Kaplan–Meier survival curve (TCR4 n = 20, Flu TCR n = 10, PBS n = 10). *** P < 0.001 and NS using log-rank test. D, day; NS, not significant.

Article Snippet: The complex was freshly prepared by incubating recombinant human IL-15 (Miltenyi Biotec) with IL-15R-α-Fc (R&D Systems) at a 1:1 molar ratio for 30 minutes at 37 °C and administered at the final concentration of 1 μg of IL-15 per mouse.

Techniques: In Vivo, Injection, Transduction