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Allografting

Optimizing a photoallodepletion protocol for adoptive immunotherapy after haploidentical SCT

Bone Marrow Transplantation volume 47, pages 1196–1200 (2012)Cite this article

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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.

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Acknowledgements

We thank KIADIS Pharma for purchasing TH9402 and device for photodynamic purging procedure and Dr Geraldine Anne Boyd for editorial assistance. This study was supported by grants from the Italian Association for Cancer Research, the Italian Ministry of Further Education and the Italian Ministry of Health, by a Translational Research Grant from the Leukemia and Lymphoma Society, by the European Community ‘Allostem’ Project (Contract number: 503319) and by the National Institutes for Health of the USA (Project Number 1 PO1 CA 100265-01A1). KP is the recipient of the Piero Martino Fellowship for Infectious complications in Hematological Malignancies of the Italian Society of Experimental Hematology.

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Authors and Affiliations

  1. Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy

    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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  1. K Perruccio
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  2. F Topini
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  3. A Tosti
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  4. A Carotti
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  6. L Ruggeri
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  7. A Mancusi
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  8. E Urbani
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  9. F Aversa
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  10. M F Martelli
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  11. A Velardi
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Correspondence to K Perruccio.

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Perruccio, K., Topini, F., Tosti, A. et al. Optimizing a photoallodepletion protocol for adoptive immunotherapy after haploidentical SCT. Bone Marrow Transplant 47, 1196–1200 (2012). https://doi.org/10.1038/bmt.2011.237

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