SPECIFIC DEPLETION OF ALLOREACTIVITY AGAINST HAPLOTYPE MISMATCHED RELATED INDIVIDUALS BY A RECOMBINANT IMMUNOTOXIN - A NEW APPROACH TO GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS IN HAPLOIDENTICAL BONE-MARROW TRANSPLANTATION

Citation
Da. Mavroudis et al., SPECIFIC DEPLETION OF ALLOREACTIVITY AGAINST HAPLOTYPE MISMATCHED RELATED INDIVIDUALS BY A RECOMBINANT IMMUNOTOXIN - A NEW APPROACH TO GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS IN HAPLOIDENTICAL BONE-MARROW TRANSPLANTATION, Bone marrow transplantation, 17(5), 1996, pp. 793-799
Citations number
34
Categorie Soggetti
Hematology,Oncology,Immunology,Transplantation
Journal title
ISSN journal
02683369
Volume
17
Issue
5
Year of publication
1996
Pages
793 - 799
Database
ISI
SICI code
0268-3369(1996)17:5<793:SDOAAH>2.0.ZU;2-Y
Abstract
Haploidentical bone marrow transplantation (BMT) is associated with a high risk of severe graft-versus-host disease (GVHD), While pan-T cell depletion of the graft is the most effective means of preventing seve re GVHD, it is associated with delayed recovery of T cell function lea ding to fatal infections, We used two related Pseudomonas exotoxin-bas ed immunotoxins, anti-Tac(Fv)-PE38 and anti-Tac(Fv)-PE38KDEL, that bot h target the IL-2 receptor on activated T cells, to specifically deple te alloreactive lymphocytes against haploidentical stimulators, The fu nctional capacity of the remaining lymphocytes was tested in prolifera tive assays against the original haploidentical stimulator and pooled cells from other mismatched donors (third party), We varied the recomb inant toxin concentration and schedule to determine the optimum condit ions for selective depletion, In 10 experiments, the mean residual rea ctivity after depletion was 7.6 +/- 1.4% against the haploidentical st imulator and 64.2 +/- 5% against the third party, expressed as a perce ntage of the undepleted response to the same stimulators, Depletion wa s shown to be specific for mixed lymphocyte culture (MLC)-activated ly mphocytes, The immunotoxin did not affect CFU-GM growth of normal BM c ells, This selective depletion of haploidentical alloreactivity could be used to prevent GVHD while conserving immune recovery following hap loidentical BMT.