Fig. 5.
Combination CD47 and PD-L1 blockade potentiates the vaccinal effect of antitumor antibody immunotherapy against syngeneic B16-F10 tumors. (A and B) Combined (A) and individual (B) tumor growth curves, (C) disease-free survival, and (D) overall survival of C57BL/6J mice bearing s.c. B16F10 tumors treated with control nanobody (Nb) or A4 in combination with TA99 (anti–TRP-1) and anti–PD-L1 (10F.9G4). 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 the various combinations for 14 d total. Treatment was initiated on day 0 postchallenge. Surviving mice from each group (n = 2/10 in Ctr plus TA99 plus PD-L1; n = 6/10 in A4 plus TA99 plus PD-L1) were rechallenged with 5 × 105 B16F10 tumor cells on day 42 as indicated by the dashed line. The data shown are the combined primary challenge (day 0–42) and secondary challenge (day 42–65). The data shown are the mean (n = 10 per group) ± SEM and are representative of two independent experiments. Mice were euthanized when tumors reached 125 mm2, and growth curves are censored after >50% of the mice had been euthanized.