XmAbCD40 inhibits growth of established large Ramos tumors. Ramos cells (2.5 × 106) were injected subcutaneously into SCID mice. Starting on day 17 after tumor cell injection, mice bearing large tumors (200-350 mm3) were injected intraperitoneally with vehicle (PBS) or antibodies twice per week for 3 weeks, as indicated by arrows. (A) Dose-response study showing effects of XmAbCD40 at 0.6, 2, or 6 mg/kg (n = 10/group). A dose-dependent antitumor effect is evident (day 28 MTV = 2225, 723, and 0 mm3 for 0.6, 2, and 6 mg/kg, respectively; P = .0007 for 0.6 vs 2 mg/kg and P = .0004 for 2 vs 6 mg/kg), with complete tumor regression occurring in 80% of mice treated with the highest dose. (B) Study comparing antitumor activity of XmAbCD40 with anti-CD40 IgG1, rituximab, and the anti-CD40 Fc-KO, all at 6 mg/kg (n = 15/group). XmAbCD40 dramatically inhibits tumor growth compared with vehicle (day 26 MTV = 70 mm3 vs 2849 mm3, P = .000076) and is significantly more effective than rituximab (day 36 MTV = 3 mm3 vs 1500 mm3, P = .000076). By day 36, 67% of the XmAbCD40-treated mice became completely tumor-free (vs none of the rituximab-treated mice); and by day 39, 100% were tumor-free. The IgG1 analog also shows potent antitumor activity but is significantly less effective than XmAbCD40 at all but the last 2 time points (P ≤ .007 for days 24-34). The anti-CD40 Fc-KO shows no antitumor activity, indicating the importance of FcγR engagement. (C) The y-axis magnification of panel B illustrates the difference between the anti-CD40 IgG1 and XmAbCD40 responses and demonstrates the improved efficacy of XmAbCD40 mediated by increased affinity to FcγRs. Data are mean ± SEM.
