Fig. 2.

Immune effector mechanism of anti–ErbB-2 mAb therapy. (A) H2N100 tumor cells (5 × 10⁵ cells) were injected s.c. into WT and gene-targeted perforin-deficient BALB/c mice, and treated with 100 μg anti–ErbB-2 mAb (clone 7.16.4) or control Ig (clone MAC4) injected i.p. on days 12, 16, 19, and 23 (perforin^−/− + 7.16.4 vs. WT + 7.16.4, P = 1.0). In some groups, WT and perforin-deficient mice were also injected with neutralizing anti-FasL mAb (clone MLF1; P = 1.0 vs. cIg). (B) Same as A; mice were depleted of NK cells (#P = 0.0097 vs. 7.16.4 + cIg) or treated with neutralizing mAbs to TNF (clone TN3-19.12; P = 1.0), IFNAR1 (clone MAR1-5A3; *P = 0.0095 vs. 7.16.4 + cIg), or IFN-γ (clone H22; **P = 0.0095 vs. 7.16.4 + cIg; ***P = 0.031 vs. 7.16.4 + αIFN-γ). (C) Same as A, except that H2N100 tumors were established in BALB/c-MMTV-neu transgenic mice, and mice were injected with 7.16.4 or control Ig on days 8, 10, 12, 14, 16, 18, 20, and 22 (*P = 0.0317; **P = 0.0159; ***P = 0.0079 vs. 7.16.4 + cIg). (D) Same as A except that gene-targeted, MyD88-deficient mice were used (*P = 0.0112 vs. WT + 7.16.4). (E) Same as A; mice were treated with neutralizing mAbs against IL-1R (clone JAMA147; results of one of two representative experiments are shown). (F) Same as A; WT or gene-targeted IL-4–deficient, IL-13–deficient, or IFN-γ–deficient mice were used. WT mice were treated with neutralizing mAbs against IL-17Rα (clone M751; results of one of two representative experiments are shown). Data are mean ± SE of five mice per group. Statistical analyses were performed at the time points indicated in figure using the Mann–Whitney test. Depleting or neutralizing mAbs were injected i.p. on days 11, 12, 19, and 26.