Pseudomonas exotoxin-based immunotoxins containing the antibody LL2 or LL2-Fab' induce regression of subcutaneous human B-cell lymphoma in mice

摘要: We have produced immunotoxins using LL2, a monoclonal antibody which binds to human B-cell lymphomas and which, in radioiodinated form, induced responses lymphoma patients (D. M. Goldenberg et al. , J. Clin. Oncol., 9: 548–564, 1991). coupled LL2 Lys-PE38KDEL, derivative of Pseudomonas exotoxin (PE) does not bind the PE receptor. LL2-PE38KDEL was cytotoxic toward several Burkitt's lines, with 50% inhibitory concentration values ranging from 2 6 ng/ml (10–30 pm). Another immunotoxin, LL2-Fab'-PE38KDEL, by chemically coupling Fab' fragment Lys-PE38KDEL. LL2-Fab'-PE38KDEL also cells, 1–2 (13–24 The alone had no cytotoxicity malignant excess prevented LL2-Fab'-PE38KDEL. Control UPC-10-PE38KDEL Mu-9-Fab'-PE38KDEL were cytotoxic. bound cells 17% affinity respectively. Both immunotoxins, but UPC-10-PE38KDEL, development CA-46 tumors nude mice. control led complete regressions measurable s.c. mice, when given at 35% lethal dose, significantly retarded growth did cause tumor regressions. Immunotoxins containing derivatives can be targeted merit further study as potential therapeutic agents.