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
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
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.