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- Title
Optimizing a photoallodepletion protocol for adoptive immunotherapy after haploidentical SCT.
- Authors
Perruccio, K; Topini, F; Tosti, A; Carotti, A; Burchielli, E; Ruggeri, L; Mancusi, A; Urbani, E; Aversa, F; Martelli, M F; Velardi, A
- Abstract
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 H3-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.
- Subjects
IMMUNOTHERAPY; HAPLOTYPES; T cells; GRAFT versus host disease; HEMATOPOIETIC stem cell transplantation
- Publication
Bone Marrow Transplantation, 2012, Vol 47, Issue 9, p1196
- ISSN
0268-3369
- Publication type
Article
- DOI
10.1038/bmt.2011.237