This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Montagna, D. Articles by Maccario, R. Search for Related Content PubMed PubMed Citation Articles by Montagna, D. Articles by Maccario, R.

Single-Cell Cloning of Human, Donor-Derived Antileukemia T-Cell Lines for In vitro Separation of Graft-versus-Leukemia Effect from Graft-versus-Host Reaction

¹ Department of Pediatrics, Laboratory of Immunology, University of Pavia; and ² Pediatric Hematology-Oncology Unit and Laboratory of Immunology, Pediatric Hematology-Oncology Unit, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy

Requests for reprints: Daniela Montagna, Dipartimento di Scienze Pediatriche, Università di Pavia, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, P. le Golgi 2, 27100 Pavia, Italy. Phone: 39-0382-502603; Fax: 39-0382-501251; E-mail: d.montagna{at}smatteo.pv.it.

In previous studies, we showed the possibility of expanding in vitro polyclonal CTL lines directed against patient leukemia cells using effector cells derived from both HLA-matched and HLA-mismatched hematopoietic stem cell donors. Some CTL lines, especially those derived from an HLA-disparate donor, displayed residual alloreactivity against patient nonmalignant cells. In this study, we evaluated the possibility of separating in vitro CTLs with selective graft-versus-leukemia (GVL) activity from those potentially involved in the development of graft-versus-host disease (GVHD) through single T-cell cloning of antileukemia polyclonal CTL lines. We showed that CTLs that were expanded from a single T-cell clone (TCC), able to selectively kill leukemia blasts and devoid of alloreactivity towards nonmalignant cells, can be obtained from antileukemia alloreactive polyclonal CTL lines. TCCs expressed a wide repertoire of different T-cell receptor (TCR)-Vß families, mainly produced IFN and interleukin 2, irrespective of CD8 or CD4 phenotype, and could be extensively expanded in vitro without losing their peculiar functional features. The feasibility of our approach for in vitro separation of GVL from GVH reaction opens perspectives for using TCCs, which are selectively reactive towards leukemia blasts, for antileukemia adoptive immune therapy approaches after hematopoietic stem cell transplantation, in particular from HLA-mismatched donors. (Cancer Res 2006; 66(14): 7310-6)

This article has been cited by other articles:

				M. Stern, L. Ruggeri, A. Mancusi, M. E. Bernardo, C. de Angelis, C. Bucher, F. Locatelli, F. Aversa, and A. Velardi Survival after T cell-depleted haploidentical stem cell transplantation is improved using the mother as donor Blood, October 1, 2008; 112(7): 2990 - 2995. [Abstract] [Full Text] [PDF]

				I. Jedema, P. Meij, E. Steeneveld, M. Hoogendoorn, B. A. Nijmeijer, M. van de Meent, S. A.P. van Luxemburg-Heijs, R. Willemze, and J.H. F. Falkenburg Early Detection and Rapid Isolation of Leukemia-Reactive Donor T Cells for Adoptive Transfer Using the IFN-{gamma} Secretion Assay Clin. Cancer Res., January 15, 2007; 13(2): 636 - 643. [Abstract] [Full Text] [PDF]