Fig. 4.
CD47 antagonism enhances the efficacy of anti–PD-L1 checkpoint blockade therapy but not antitumor antibody or whole-cell vaccination immunotherapy against syngeneic B16-F10 tumors. (A and B) Growth and survival of C57BL/6J mice bearing s.c. B16-F10 tumors treated with control nanobody (Nb), anti-CD47 Nb A4, and/or TA99. Treatment was initiated on day 4 postchallenge. (C and D) Growth and survival of C57BL/6J mice bearing s.c. B16-F10 tumors treated with GVAX and control Nb or GVAX and A4. Treatment was initiated on day 0 postchallenge, and GVAX was administered s.c. on days 0, 4, and 7. Nb was administered daily for 14 d. (E and F) Growth and survival of C57BL/6J mice bearing s.c. B16-F10 tumors treated with control Nb, A4, and/or anti–PD-L1 blocking antibody (10F.9G4). Treatment was initiated on day 0 postchallenge. The data shown in all panels are the mean (n = 10/group) ± SEM and are representative of at least two independent experiments. In all experiments, mice were challenged with 5 × 105 B16F10 cells by s.c. injection and received daily i.p. injections of control Nb or A4 (200 μg), every other day injections of TA99 or anti–PD-L1 (250 μg), or various combinations for 14 d total. Mice were euthanized when tumors reached 125 mm2, and growth curves are censored after >50% of the mice had been euthanized.