MURINE MONOCLONAL ANTI-T CELL ANTIBODIES FOR TREATMENT OF STEROID-RESISTANT ACUTE GRAFT-VERSUS-HOST DISEASE

Four different murine monoclonal anti-T cell antibodies were administered to 15 patients with severe steroid resistant graft vs. host disease (GVHD) in a phase I clinical trial to evaluate feasibility ant toxicity. Antibodies 9.6 (IgG2a) and 35.1 (IgG2a) bind to separate epitopes on the E receptor (Tp50); antibody 10.2 (IgG2a) binds to the murine Lyt-1 homolog (Tp67); and antibody 12.1 (IgG2a) binds to a cell surface antigen with a MW of .apprx. 100,000 daltons (Tp100). A total of 151 infusions were given, ranging in dose from 1-20 mg, each administered over a 1-4 period. One patient received a total of 259 mg of antibody over a period of 45 days. Six infusions (4%) in 2 patients were associated with fever or fever and chills. By decreasing the infusion rate, subsequent infusions to these 2 patients were accomplished without additional reactions. Although most of the patients treated with monoclonal antibodies required platelet support, the number of platelet units given was not significantly different from similar patients not receiving monoclonal antibodies. Six of 10 patients receiving intermediate to high doses (5-20 .mu.g) antibody therapy had evidence of at least partial improvement in GVHD in at least 1 involved organ system. None of the patients became immunized to mouse Ig. Therapy of GVHD with murine monoclonal anti-T antibodies in feasible and these antibodies apparently can be administered to marrow transplant patients without significant toxicity. Further studies are required to determine which antibodies or combinations of antibodies have optimal anti-GVHD effect.