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. 2013 May 15;123(6):2590–2603. doi: 10.1172/JCI65624

Figure 7. Antibodies against p55TNFR protect against TNF toxicity, increase MTD, and allow safe anticancer therapy.

Figure 7

(A) TNF (30 mg) was administered to mice pretreated i.p. with different doses of anti-mp55TNFR monoclonal antibodies (10 mg/ml, n = 5; 5 mg/ml, n = 5; 2.5 mg/ml, n = 4) or PBS (n = 7) or control hamster IgG1 (10 mg/ml, n = 5). (B) Antitumor effects and (C) survival in antitumor experiments on Tnfrsf1a+/+ mice treated for 10 days paralesionally with TNF (25 mg) plus IFN-γ (5,000 IU) (black symbols) or PBS (white symbols) and cotreated i.p. daily with PBS (black), control (red), or anti-mp55TNFR antibodies (gray). (D) Toxicity study of TNF/IFN-γ in B16BL6 melanoma-bearing Tnfrsf1a+/+ mice cotreated i.p. with PBS, control antibodies, or anti-mp55TNFR antibody for 10 days. (E) Human TNFRSF1A knockin mice treated i.p. with anti-hp55TNFR monoclonal antibodies (10 mg/ml, n = 6 or 4 mg/ml, n = 6) or control antibody (10 mg/ml, n = 6) and injected with 50 mg TNF or PBS (n = 6). (F) Antitumor effects and (G) survival in antitumor experiments in human TNFRSF1A knockin mice treated with PBS (white symbols) or TNF/IFN-γ (black symbols) and daily i.p. coadministration of PBS (n = 6), control (n = 6), or anti-hp55TNFR antibodies (n = 12). (H) Toxicity study of TNF/IFN-γ in B16BL6 melanoma-bearing human TNFRSF1A knockin mice i.p. cotreated with PBS, control antibody, or anti hp55TNFR antibody. The horizontal line in D and H represents LD50. In the TSI graphs, “***” is between PBS and TNF/IFN-γ–treated p55TNFR antibody groups. All data represent mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 (Student’s t test in B and F and log-rank test in A, C, E, and G).