THE USE OF AN ANTI-CD3 IMMUNOTOXIN TO PREVENT THE DEVELOPMENT OF LYMPHOPROLIFERATIVE DISEASE IN SCID PBL MICE/

Severe combined immunodeficient mice (SCID) reconstituted with normal PBLs (SCID/PBL) from Epstein-Barr virus-positive (EBV+) human donors o ften develop fatal human B lymphomas which resemble the EBV-induced ly mphoproliferative disease (LPD) observed in immunosuppressed individua ls. This phenomenon appears to be T cell dependent. In this study we u sed an immunotoxin (IT) prepared by conjugating the monoclonal anti-CD 3 antibody, 64.1, to deglycosylated ricin A chain (dgRTA) to prevent L PD in SCID/PBL mice. We show that the incidence of LPD is greatly redu ced by either a combination of in vitro treatment of PBLs followed by one in vivo treatment of the xenografted mice with 64.1-dgRTA immunoto xin or by repeated treatments in vivo with the immunotoxin. In contras t, in vitro treatment alone or in vivo treatment with only one injecti on of 64.1-dgRTA were less effective. As expected, this IT did not hav e any non-specific cytotoxic effects on already established EBV+ tumor s from SCID/PBL mice. The use of this rr, therefore, represents a simp le method to avoid LPD when injecting blood-containing tissues into SC ID mice. (C) 1998 Elsevier Science B.V. All rights reserved.