Figure 1.
Tolerogenic anti-IL-2 mAb (JES6-1A12) but not non-tolerogenic anti–IL-2 mAb (S4B6) prevents aGVHD and preserves GVL activity more effectively than TAC. (A-D) Lethally irradiated WT BALB/c recipients were given splenocytes (5 × 106) with or without TCD-BM cells (2.5 × 106) from WT C57BL/6 donors. Recipients were given a total of 4 i.p. injections of rat-IgG, anti–IL-2 mAb (JES6-1A12), or anti–IL-2 mAb (S4B6) (500 µg/mouse) at days 0, 2, 4, and 6 after HCT. (A,C) Plots of percent original body weight, diarrhea, and percent survival are shown. n = 7-8 combined from 2 replicated experiments. (B,D) Mean ± standard error of the mean of histopathology scores of liver, small intestine, and colon are shown; n = 4 per group. Combined from 2 replicated experiments. (E) WT BALB/c recipients given splenocytes and TCD-BM cells from WT C57BL/6 donors and injected IgG or anti–IL-2 mAb (JES6-1A12) as described in panels A-D. Recipients were challenged with i.p. injection of BCL1/Luc cells (5 × 106/mouse) on day 0. Mice were monitored for tumor growth by using in vivo bioluminescent imaging (BLI), clinical signs of GVHD, and survival. One representative BLI image from each time point is shown for each group and summary of photons/second, diarrhea, and tumor-free survival of recipients. n = 8 combined from 2 replicated experiments. (F) Lethally irradiated WT BALB/c recipients were given splenocytes (2.5 × 106) and TCD-BM cells (2.5 × 106) from WT C57BL/6 donors. Recipients were challenged with i.p. injection of BCL1/Luc cells (5 × 106/mouse) on day 0 and were given a total of 4 i.p. injections of anti–IL-2 mAb (JES6-1A12) (500 µg/mouse) at days 0, 2, 4, and 6 after HCT, or daily i.p. injections of TAC (0.75 mg/kg) at days 0 to 21 after HCT. One representative BLI image from each time point is shown for the anti–IL-2 mAb (JES6-1A12) and TAC group and summary of photons/second, body weight change, as well as the tumor-free survival of recipients. n = 8-10 combined from 2 replicated experiments. (G) Lethally irradiated BALB/c recipients were given splenocytes (1.25 × 106) and TCD-BM cells (2.5 × 106) from C57BL/6 donors. Recipients were challenged with i.p. injection of BCL1/Luc cells (10 × 106/mouse) on day 0 and were given a total of 4 intravenous injections of IL-2 mAb (500 µg/mouse) at days 0, 2, 4, and 6 after HCT, or i.p. injections of TAC (0.75 mg/kg) once daily until moribund with tumor growth. One representative BLI image from each time point is shown for IL-2 mAb (JES6-1A12) and TAC group and summary of photons/second and tumor-free survival of recipients. n = 8-10 combined from 2 replicated experiments. “+” indicates death. Data represent mean ± standard error. P values were calculated by using ordinary one-way analysis of variance (panels B,D), two-tailed Student t tests (panels F,G), or log-rank test for survival comparison (panels A,E-G). *P < .05, **P < .01, ***P < .001, ****P < .0001.

Tolerogenic anti-IL-2 mAb (JES6-1A12) but not non-tolerogenic anti–IL-2 mAb (S4B6) prevents aGVHD and preserves GVL activity more effectively than TAC. (A-D) Lethally irradiated WT BALB/c recipients were given splenocytes (5 × 106) with or without TCD-BM cells (2.5 × 106) from WT C57BL/6 donors. Recipients were given a total of 4 i.p. injections of rat-IgG, anti–IL-2 mAb (JES6-1A12), or anti–IL-2 mAb (S4B6) (500 µg/mouse) at days 0, 2, 4, and 6 after HCT. (A,C) Plots of percent original body weight, diarrhea, and percent survival are shown. n = 7-8 combined from 2 replicated experiments. (B,D) Mean ± standard error of the mean of histopathology scores of liver, small intestine, and colon are shown; n = 4 per group. Combined from 2 replicated experiments. (E) WT BALB/c recipients given splenocytes and TCD-BM cells from WT C57BL/6 donors and injected IgG or anti–IL-2 mAb (JES6-1A12) as described in panels A-D. Recipients were challenged with i.p. injection of BCL1/Luc cells (5 × 106/mouse) on day 0. Mice were monitored for tumor growth by using in vivo bioluminescent imaging (BLI), clinical signs of GVHD, and survival. One representative BLI image from each time point is shown for each group and summary of photons/second, diarrhea, and tumor-free survival of recipients. n = 8 combined from 2 replicated experiments. (F) Lethally irradiated WT BALB/c recipients were given splenocytes (2.5 × 106) and TCD-BM cells (2.5 × 106) from WT C57BL/6 donors. Recipients were challenged with i.p. injection of BCL1/Luc cells (5 × 106/mouse) on day 0 and were given a total of 4 i.p. injections of anti–IL-2 mAb (JES6-1A12) (500 µg/mouse) at days 0, 2, 4, and 6 after HCT, or daily i.p. injections of TAC (0.75 mg/kg) at days 0 to 21 after HCT. One representative BLI image from each time point is shown for the anti–IL-2 mAb (JES6-1A12) and TAC group and summary of photons/second, body weight change, as well as the tumor-free survival of recipients. n = 8-10 combined from 2 replicated experiments. (G) Lethally irradiated BALB/c recipients were given splenocytes (1.25 × 106) and TCD-BM cells (2.5 × 106) from C57BL/6 donors. Recipients were challenged with i.p. injection of BCL1/Luc cells (10 × 106/mouse) on day 0 and were given a total of 4 intravenous injections of IL-2 mAb (500 µg/mouse) at days 0, 2, 4, and 6 after HCT, or i.p. injections of TAC (0.75 mg/kg) once daily until moribund with tumor growth. One representative BLI image from each time point is shown for IL-2 mAb (JES6-1A12) and TAC group and summary of photons/second and tumor-free survival of recipients. n = 8-10 combined from 2 replicated experiments. “+” indicates death. Data represent mean ± standard error. P values were calculated by using ordinary one-way analysis of variance (panels B,D), two-tailed Student t tests (panels F,G), or log-rank test for survival comparison (panels A,E-G). *P < .05, **P < .01, ***P < .001, ****P < .0001.

Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal