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Optimizing a photoallodepletion protocol for adoptive immunotherapy after haploidentical SCT.
MedLine Citation:
PMID:  22139067     Owner:  NLM     Status:  Publisher    
In adults, one-haplotype-mismatched haematopoietic SCT (haploidentical HSCT) is associated with slow immune recovery due to decaying thymic function and extensive T-cell depletion of the graft. Although essential for preventing GVHD, T-cell depletion underlies the major reasons for transplant failure: leukemia relapse and infections, with infection-related mortality accounting for about 40% of non-leukemic deaths. Adoptive T-cell therapy would be helpful for these patients but to administer it without causing GVHD, alloreactive T cells need to be eliminated from donor T lymphocytes before infusion. In a preclinical study, to address this problem, we determined the efficacy of photodynamic purging of alloreactive T cells, by investigating combinations of parameters in order to achieve maximum allodepletion, preservation of T-regulatory cells and of pathogen and leukemia-specific T-cell responses in donor-vs-recipient MLR. We also needed to identify an optimal method to quantify the Ag-specific T-cell repertoires. Optimal procedures were identified. In particular, we compared limiting-dilution analyses (LDA) of proliferating T cells with H(3)-thymidine incorporation by bulk T cells and with flow cytometry CD25 expression, which is accepted as a T-cell activation marker. This study demonstrated that LDA is a reliable, predictable and sensitive method for measuring alloreactive, pathogen- and leukemia-specific T-cell frequencies.Bone Marrow Transplantation advance online publication, 5 December 2011; doi:10.1038/bmt.2011.237.
K Perruccio; F Topini; A Tosti; A Carotti; E Burchielli; L Ruggeri; A Mancusi; E Urbani; F Aversa; M F Martelli; A Velardi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-05
Journal Detail:
Title:  Bone marrow transplantation     Volume:  -     ISSN:  1476-5365     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8702459     Medline TA:  Bone Marrow Transplant     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.
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