CD3 immunotoxin therapy of cutaneous T cell lymphoma

e19511 Background: T cell lymphomas represent 12% of lymphoma cases in the U.S. Cytotoxic chemotherapies, radiation therapies, monoclonal antibodies, transcription modulators and topical therapies yield remissions, but over half of patients relapse and die with progressive disease. Patients ineligible for allogeneic transplant need additional therapeutic options. One class of T cell directed agents are immunotoxins composed of protein synthesis inactivating peptide toxins covalently linked to antibodies or hormone ligands. We prepared a new immunotoxin, A-dmDT390-bisFv(UCHT1) composed of the catalytic and translocation domains of diphtheria toxin fused to two single chain antibody fragments reactive with an acidic loop on the extracellular domain of CD3epsilon. We prepared a clinical batch of drug and obtained FDA approval for a phase I trial (IND#100712). Methods: Cohort of three-six CTCL patients were treated with immunotoxin via 15min IV infusion twice daily for four days at 2.5–5ug/kg. CTCAEv3.0 toxic...