Figure 8. Cytokine-mediated tumour immunotherapy.
(a) In vivo cytotoxicity for YAC-1 lymphoblast cell line after intravenous injection of tumour into A/J mice treated with 200,000 IUe of cytokine or OMCP-mutIL-2 construct. Comparison performed by unpaired t-test between groups as indicated by the lines above the graphs. (b) In vitro lysis of YAC-1 lymphoma by bulk A/J splenocytes after 200,000 IUe of cytokine or OMCP-mutIL-2 construct treatment. (c) LLC flank growth after cytokine treatment of wild-type C57BL/6 mice. Treatment with 750,000 IUe of cytokine or fusion construct was started on day 5-post tumour injection, after palpable tumors were evident, and continued through day 10 in 10 equal doses of 75,000 IUe/dose. Raw data are shown in Supplementary Data 1 and represents 6 mice in the saline group and 5 in the wtIL-2, mutIL-2 and OMCP-mutIL-2 group. (d) LLC tumour growth in C57BL/6 mice depleted of NK1.1 cells or (e) mutant mice deficient in NKG2D. Data representative of 5 mice per group for both NK1.1 depleted and NKG2D deficient mice. (f) LLC tumour growth in C57BL/6Rag1−/− mice. Data representative of 5 mice per group. Comparison performed by multiple unpaired t-tests at each individual time point to saline-treated controls for all tumour growth experiments. (g) Survival of C57BL/6 mice treated with 750,000 IUe of cytokine 5 days after injection of 1 × 105 LLC intravenously. Data extrapolated from groups consisting of 7 mice in the wtIL-2 and mutIL-2 treated groups and 8 mice from the saline and OMCP-mutIL-2 treated groups. Cytokines or OMCP-mutIL-2 fusion protein was given as ten doses on days 5–10 post tumor injection with A/J mice receiving a total of 200,000 IUe and C57BL/6 mice receiving 750,000 IUe. Kaplan–Meier survival graphs were compared by Log-rank (Mantel–Cox) test. ns P>0.05; *P<0.05; **P<0.01; ***P<0.001; black=saline; blue=wtIL-2, red=OMCP-mutIL-2, green=mutIL-2.