Inhibitory Effect Of TJU103 On Graft-Versus-Host Disease After Allogeneic Bone Marrow Transplantation

Objective: The efficacy of TJUIO3, a small organic compound, was investigated in mw-inc models of graft-versus-host disease(GVLID), with the intention of developing a new anti-GVHD drug. Method: 1. To induce lethal (IIVHD after bone marrow transplantation in MHC-full-mismatched murine model and in MHC-haplo-identical murine model, recipients BALB/c and CB6F 1 were conditioned by lethal total body irradiation (9.0 Gy) and transplanted with donor C57BL/6 bone marrow plus spleen cells. 2. The efficacy of TJU1O3 on proliferative response of T cell was investigated in mixed lymphocyte culture. 3. The potential of TJU1O3 for suppressing the developing of GVHD was evaluated in C57BL/6-BALB/c, and C57BL/6CB6F1 models. Results: 1. Transplantation with 4.5 x 106 bone marrow cells plus 3 x ~ 0拁 spleen cells from donors C57BLI6 mice induced lethal GVHD in MI-IC-full-mismatched murine model and in MHIC-baplo-identical murine model. All mice developed classic GV7HD and died by day 17 posttransplant. 2. TJU 103 exhibited a dose-dependent inhibitory effect on proliferation of T cells in MLR. Nearly 83% inhibition of the proliferative response was observed with the addition of 2511 g/ml of TJU1O3. 3. Treament with daily injection of TJU1O3(50 1.1 glinjection) for the first one week protected mice from GVHD. In the M}IC-full-mismatched model, the survival rate on day 30 was 0% in the untreated group versus 80% in the treated group(P < 0.01). The MST was 15 days in the untreated group versus 30 days in the treated group(P < 0.05). In the MHC-haplo-identical model, the survival rate on day 30 was 0% in the untreated group versus 90% in the treated group(P < 0.01). The MST was 14 days in the untreated group versus 30 days in the treated group(P < 0.05). Conclusions: 1. C57BL16 - BALBIc, C57BL16 - CB6F1 are classic MHC-full-mismatched and MHC-haplo-identical (IVHD animal models, respectively. 2. TJU1O3 is capable of inhibiting T cells proliferative response markedly in vitro. 3. The administration of TJU1O3 is an efficacious approach against the development of GVHD.