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 often develop fatal human B lymphomas which resemble the EBV-induced lymphoproliferative disease (LPD) observed in immunosuppressed individuals. This phenomenon appears to be T cell dependent. In this study we used an immunotoxin (IT) prepared by conjugating the monoclonal anti-CD3 antibody, 64.1, to deglycosylated ricin A chain (dgRTA) to prevent LPD in SCID/PBL mice. We show that the incidence of LPD is greatly reduced by either a combination of in vitro treatment of PBLs followed by one in vivo treatment of the xenografted mice with 64.1-dgRTA immunotoxin or by repeated treatments in vivo with the immunotoxin. In contrast, in vitro treatment alone or in vivo treatment with only one injection of 64.1-dgRTA were less effective. As expected, this IT did not have any non-specific cytotoxic effects on already established EBV⁺ tumors from SCID/PBL mice. The use of this IT, therefore, represents a simple method to avoid LPD when injecting blood-containing tissues into SCID mice.