A humanized non–FcR-binding anti-CD3 antibody, visilizumab, for treatment of steroid-refractory acute graft-versus-host disease

Abstract

Visilizumab is a humanized anti-CD3 monoclonal antibody characterized by a mutated IgG2 isotype, lack of binding to Fc␥-receptors, and ability to induce apoptosis selectively in activated T cells. To test pharmacokinetics, safety, and immunosuppressive activity of visilizumab, 17 patients with glucocorticoid-refractory acute graft-versus-host disease (GVHD) were enrolled in a phase 1 study. Six patients were given 7 doses of visilizumab (

Mycophenolate mofetil for the management of steroid-refractory acute graft vs host disease

“…Additionally, OS reported here is within the range of reported survival among alternative agents used for steroidrefractory aGVHD. [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] MMF was overall well tolerated, with the majority of those treated here remaining on therapy without dose reduction or significant adverse events directly referable to this agent; only two patients required discontinuation of MMF on account of myelosuppression. However, though a direct causal role cannot be assigned to MMF, the overall burden of immunosuppression and related infectious complications certainly contributed to the morbidity and mortality seen in this series.…”

“…5,[8][9][10][11] A number of therapeutic agents directed at the immune cascade underlying aGVHD have shown modest activity in steroid-refractory aGVHD. [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] Mycophenolate mofetil (MMF), whose metabolite mycophenolic acid inhibits the de novo synthesis of purines in lymphocytes, has probable efficacy in the treatment of aGVHD, based on three small case series that cumulatively reported 17 cases in which MMF was used for initial therapy for aGVHD, and 16 cases with glucocorticoidrefractory aGVHD. [31][32][33] Here, we report outcomes in a series of 27 recipients of allogeneic hematopoietic cell transplantation treated with MMF as salvage therapy for steroid-refractory aGVHD.…”

Proinflammatory cytokines and their role in the development of major transplant-related complications in the early phase after allogeneic bone marrow transplantation

“…32 Anti-T-cell antibodies such as antithymocyte globulins have been used for pre-emptive treatment of AGVHD in high-risk patients. 33 Monoclonal antibodies directed against activated T cells such as visilizumab 34 or ABX-CBL 35 have been used successfully to treat steroid-refractory AGVHD. The use of anticytokines in AGVHD has thus far been disappointing, mainly because of initiating therapy at advanced stages and recurrence of AGVHD after stopping the treatment.…”

Treatment of steroid-resistant acute graft-versus-host disease with daclizumab and etanercept

“…One treatment option is based on drugs, which are directly cytotoxic to the effector cells of aGVHD (ATG, OKT3, visilizumab, mycophenolate mofetil (MMF), pentostatin, sirolimus, anti-CD147, photopheresis). [2][3][4][5][6][7][8][9][10][11][12][13] A different approach is based on blockage of cytokines involved in the pathogenesis of aGVHD (antibodies against TNF and IL-2 or IL-1 antagonist).…”