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.
Clinchy
B
B
Cancer Immunobiology Center and Department of Microbiology, University of Texas Southwestern Medical Center at Dallas, 75235-8576, USA.
Vitetta
E S
ES
D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D005260:Female; D006566:Herpesviridae Infections; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D000922:Immunotoxins / Q000494:pharmacology / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion; D016393:Lymphoma, B-Cell; D008232:Lymphoproliferative Disorders / Q000401:mortality / Q000517:prevention & control*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D012276:Ricin / Q000494:pharmacology / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014412:Tumor Virus Infections
D017252:CD3 Complex; D007136:Immunoglobulins; D000922:Immunotoxins; D012276:Ricin