IMMUNOTOXINS CONTAINING SAPORIN LINKED TO DIFFERENT CD2 MONOCLONAL-ANTIBODIES - IN-VITRO EVALUATION

In this study we describe immunotoxins prepared with different CD2 mon oclonal antibodies (mAbs) and a ribosome-inactivating protein, saporin . The CD2 immunotoxins were tested on different models. Anti-CD2-sapor in conjugates inhibited protein synthesis by a neoplastic CD2+ cell li ne (SKW-3) and by an interleukin 2 dependent polyclonal CD2+ lymphoid cell culture (T lymphoblasts), with IC(50)s ranging from 10(-13) M to 10(-11) M (as saporin). Similar results were obtained with proliferati on inhibition tests (H-3-thymidine incorporation) on phytohaemagglutin in (PHA) driven lymphoid cultures and on mixed lymphocyte culture acti vated lymphocytes. Moreover a CD2-ricin A chain conjugate was less eff ective than an analogous immunotoxin containing the same CD2 mAb and s aporin in inhibiting lymphocyte proliferation induced by PHA (IC50 app roximately 10(-9) m as ricin A chain versus 10(-12) m as saporin). The conjugates were not toxic on bone marrow stem cells. These results su ggest that CD2-saporin immunotoxins could represent an effective tool for CD2+ lymphomas or leukaemias, and for T-dependent immune disorders , such as transplanted organ rejection and graft-versus-host disease.