INVIVO T-CELL ABLATION BY A HOLO-IMMUNOTOXIN DIRECTED AT HUMAN CD3

We have evaluated the in vivo efficacy of anti-CD3-CRM9, a holo-immuno toxin constructed with a diphtheria toxin binding-site mutant. Eighty percent of established human T-cell subcutaneous tumors in nude mice c ompletely regressed following intraperitoneal injection of immunotoxin at a dose set at half the minimum lethal dose assayed in toxin-sensit ive animals. Similar regressions produced by a Cs-137 source required a dose in excess of 500 cGy. The high degree of in vivo T-cell ablatio n produced by this immunotoxin is apparently due to maintenance of the toxin translocation function provided by CRM9 and a necessary intrace llular routing function supplied by CD3. This immunotoxin may be usefu l in treating conditions caused by pathologic oligoclonal T-cell expan sion such as graft-versus-host disease, autoimmune diseases, and possi bly AIDS.