Verotoxin targets lymphoma infiltrates of patients with post-transplant lymphoproliferative disease

Post-transplant lymphoproliferative disease (PTLD) is an invasive, EBV expr essing B lymphoma and a major cause of morbidity and mortality following or gan transplantation. Presently there is limited therapy available; rather t he patient often loses the allograft or succumbs to the malignancy. CD77 (o r globotriaosyl ceramide -Gb(3)) is a germinal center B cell marker [Gregor y et al. Int J Cancer 1998;42:213-20; Gregory et al., J Immunol 1987;139:31 3-8; Mangeney et al. Eur J Immunol 1991;21:1131-40], expressed on most EBV infected B cells and is the receptor for the E. coli derived verotoxin (VT) [Lingwood CA. Advances in Lipid Research 1993;25:189-212]. We present the basis of a possible novel approach to PTLD therapy utilizing the specific t argeting of VT to the infiltrating lymphoma cells. Biopsies of adenoid, kid ney or liver tissue of four PTLD patients were stained with verotoxin to de termine expression of CD77. VT is a potent inducer of necrosis/apoptosis of receptor positive cells. In each PTLD case, the infiltrating EBV positive B lymphoma cells were strongly and selectively stained with VT, identifying CD77 as a new marker for these cells. For such individuals, VT might provi de the basis of an approach to control their malignancy. (C) 2000 Elsevier Science Ltd. All rights reserved.