REVIEW On the use of donor-derived iNKT cells for adoptive immunotherapy to prevent leukemia recurrence in pediatric recipients of HLA haploidentical HSCT for hematological malignancies Paolo Dellabona a , ⁎ , Giulia Casorati a , ⁎ , Claudia de Lalla a , Daniela Montagna b , Franco Locatelli c a Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy b Laboratory of Immunology, Fondazione IRCCS Policlinico San Matteo, and Department of Pediatrics, University of Pavia, Pavia, Italy c Department of Pediatric Hematology-Oncology, IRCCS Ospedale Bambino Gesù, Roma, Italy, and University of Pavia, Pavia, Italy Received 15 September 2010; accepted with revision 24 November 2010 Available online 24 December 2010 KEYWORDS NKT cells; CD1d; Transplantation; Leukemia; Immunotherapy Abstract T-cell-depleted hematopoietic stem cell transplantation from an HLA haploidentical relative (hHSCT) is a useful therapy for children with high-risk leukemia lacking suitable HLA- matched donors. The immune deficiency ensuing hHSCT renders patients susceptible to life- threatening infections and disease recurrence. Adoptive immunotherapy can restore/enhance early post-transplantation immunocompetence of hHSCT recipients. Efforts are directed to identify strategies for inducing graft-versus-leukemia (GVL) response, while avoiding graft- versus-host disease (GVHD) occurrence. CD1d-restricted invariant iNKT cells are innate-like, lipid-reactive T lymphocytes implicated in the control of innate and adaptive immunity. Preclinical data suggest that iNKT cells positively modulate both GVL response and GVHD. Our recent findings in a cohort of 22 children given hHSCT for different hematological malignancies show that failure to reconstitute iNKT cells after transplantation correlates with leukemia relapse. In this review, we will discuss potential new options for adoptively transferring donor- derived iNKT cells into hHSCT recipients in the early post-transplantation period to prevent disease recurrence. © 2010 Elsevier Inc. All rights reserved. ⁎ Corresponding authors. Experimental Immunology Unit, Division of Immunologo, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, via Olgettina 58, 20132 Milano, Italy. Fax: +39 02 2643 4768. E-mail addresses: dellabona.paolo@hsr.it (P. Dellabona), casorati.giulia@hsr.it (G. Casorati). 1521-6616/$ - see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.clim.2010.11.015 available at www.sciencedirect.com Clinical Immunology www.elsevier.com/locate/yclim Clinical Immunology (2011) 140, 152–159