Figure 3
Optimum schedule of administration of ICOS antibody with radiation for overall survival benefit with single fraction and multi-fraction radiation. (a) (i) Experimental design. 2 × 105 CT26 cells were implanted subcutaneously in to the flanks of Balb/c mice on day 0. On day 14 all mice in radiation groups were treated with 12 Gy radiation to the tumor using CT guidance. Mice were injected i.p. with 0.25 mg/kg ICOS antibody or in Control groups, mice were treated with equivalent dose of isotype control antibody. For early treatment groups mice were treated with antibody on day 10 and day 17. For concurrent treatment groups mice were treated with antibody on day 14 and day 21. For late treatment groups mice were treated with antibody on day 18 and day 25. (ii) Average tumor growth curves for mice treated as in (i). (iii) Overall survival curves for mice treated as in (i). (b) Individual tumor growth curves for mice treated as in (a). (c) Experimental design. 1 × 106 MOC1 cells were implanted subcutaneously into the flanks of C57Bl/6 mice on day 0. On day 14 all mice in single fraction radiation groups were treated with 12 Gy radiation to the tumor using CT guidance. On days 14 and 15 all mice in dual fraction radiation groups were treated with 8 Gy per fraction radiation to the tumor using CT guidance. Mice were injected i.p. with 0.25 mg/kg ICOS antibody or in Control groups, mice were treated with equivalent dose of isotype control antibody on days 14 and day 21. (ii) Average tumor growth curves for mice treated as in (i). (iii) Overall survival curves for mice treated as in (i). (d) Individual tumor growth curves for mice treated as in (c). Statistics key for panel (a) (iii) and (c) (iii): ***p < 0.001, **p < 0.01, *p < 0.05 as determined by Log-rank test. N = 10 mice per group and experiments were repeated at least 2x.
