Figure 3. Local immunomodulation does better than systemic immunomodulation for the efficacy of antitumor immune responses.

(A) Mice were challenged s.c. with 5 × 10⁶ A20 tumor cells on the right and left flanks. Therapy was started when tumors reached 0.5–0.7 cm in diameter (usually between day 5 and 8). Treated mice received CpG i.t. only in their right tumor for 5 consecutive days. On day 1 and 5 of CpG therapy, αOX40 and αCTLA4 mAbs were either injected i.p. or i.t. (together with CpG in the right tumor). The systemic antitumor immune response generated by these systemic (i.p.) and local (i.t.) maneuvers was assessed by measuring the size of the contralateral (noninjected) left tumor and mouse disease-free survival. Results were pooled from 2 distinct experiments (n = 10 mice per group). (B) Tumor growth of the distant tumors (nontreated left tumors) when mAbs were injected systemically (i.p.) or locally (i.t. into the right tumor). Black arrows indicate day 1 of therapy. Both strategies (mAbs injected i.p. or i.t.) result in disappearance of the distant (left) tumors. (C) Relapse-free survival of mice treated with either local or systemic immunomodulation. Most of the mice treated systemically (i.p.) with αOX40/CTLA4 relapsed in the left tumor-draining lymph nodes, whereas almost all the mice who received αOX40 and αCTLA4 locally (i.t.) had a long-term survival (*P = 0.002). The number of mice per group is shown into parenthesis. (D) Therapeutic efficacy of 1:100 and 1:1,000 doses of αOX40 and αCTLA4 either injected i.p. or i.t. together with CpG and the resulting long-term disease-free survival. ttt, treatment.