Treatment of Acute Graft-Versus-Host Disease With a Nonmitogenic Anti-Cd3 Monoclonal Antibody

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

“…14,30 Accordingly, peripheral blood T-cell lymphopenia has been transient after the administration of murine anti-CD3. 31,32 Similarly, a single dose of daclizumab did not deplete CD3 ϩ CD25 ϩ peripheral blood T cells. 26 Resolution of CD8 ϩ dermal infiltrates in skin biopsies obtained from patients with skin GVHD suggests that visilizumab can induce in vivo T-cell depletion of activated pathogenic T cells.…”

“…Cells were washed in phosphate-buffered saline (PBS) and stained with antibody pairs or triplets conjugated with fluoresceinisothiocyanate (FITC), phycoerythrin (PE), or peridinin chlorophyll protein (PerCP; Becton Dickinson, San Jose, CA) and analyzed as described previously. 17 Because T-cell-bound visilizumab inhibited the binding of other anti-CD3 mAbs we identified T cells by the characteristic forward and light scatter and bright expression of CD5. Visilizumab-coated T cells were detected using FITC-conjugated F(abЈ) 2 goat antihuman IgG (Jackson Immunoresearch Labs, West Grove, PA).…”

A novel apoptosis-inducing anti-PSGL-1 antibody for T cell-mediated diseases

“…Anti-CD3 mAb has been shown to be efficacious in preventing allograft rejection and human acute GVHD [10][11][12]. However, in vivo administration of anti-CD3 antibody is associated with a deleterious clinical syndrome, which is attributed to acute release of cytokines caused by the mitogenic activity of anti-CD3 antibody [13][14][15].…”

The use of bone marrow and peripheral blood stem cell transplantation in the treatment of cancer

“…73,74 Once acute GVHD develops, it can be treated with steroids, antithymocyte globulin, and monoclonal antibodies against T cells or their receptors. [75][76][77][78] GVHD that develops or persists after three months posttransplant is termed chronic GVHD and has features in common with collagen vascular diseases, including a malar rash, sclerodermatous changes, sicca syndrome, arthritis, obliterative bronchiolitis, and, in some cases, bile duct degeneration and cholestasis. 79 Chronic GVHD develops in 20 to 40 percent of patients and is seen more often in patients with prior acute GVHD and in older patients.…”