4th Palermo Conference on INNOVATIVE THERAPIES FOR LYMPHOID MALIGNANCIES
Published online 19 May 2009
Haematologica, Vol 94, Issue 7, 967-974 doi:10.3324/haematol.2008.001339
Copyright © 2009 by Ferrata Storti Foundation
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Cell Therapy and Immunotherapy

Adoptive immunotherapy mediated by ex vivo expanded natural killer T cells against CD1d-expressing lymphoid neoplasms

Davide Bagnara1, Adalberto Ibatici2, Mirko Corselli2, Nadia Sessarego2, Claudya Tenca1, Amleto De Santanna3, Andrea Mazzarello1, Antonio Daga4, Renzo Corvò5, Giulio De Rossi6, Francesco Frassoni2, Ermanno Ciccone1, Franco Fais1

1 Human Anatomy, Department of Experimental Medicine, University of Genoa;
2 Centro Cellule Staminali e Terapia Cellulare, Ospedale San Martino, Genoa;
3 Histology Sections, Department of Experimental Medicine, University of Genoa;
4 Department of Translational Oncology and
5 Department of Otolaryngology, IST-National Cancer Research Institute, Genoa and
6 Department of Pediatric Hematology and Oncology, Ospedale Bambino Gesù, Rome, Italy

Correspondence: Franco Fais, Ph.D., Human Anatomy Section, Department of Experimental Medicine, Via De Toni, 14, 16132 Genoa, Italy, E-mail:franco.fais{at}unige.it

Background: CD1d is a monomorphic antigen presentation molecule expressed in several hematologic malignancies. Alpha-galactosylceramide ({alpha}-GalCer) is a glycolipid that can be presented to cytotoxic CD1d-restricted T cells. These reagents represent a potentially powerful tool for cell mediated immunotherapy.

Design and Methods: We set up an experimental model to evaluate the use of adoptively transferred cytotoxic CD1d-restricted T cells and {alpha}-GalCer in the treatment of mice engrafted with CD1d+ lymphoid neoplastic cells. To this end the C1R cell line was transfected with CD1c or CD1d molecules. In addition, upon retroviral infection firefly luciferase was expressed on C1R transfected cell lines allowing the evaluation of tumor growth in xenografted immunodeficient NOD/SCID mice.

Results: The C1R-CD1d cell line was highly susceptible to specific CD1d-restricted T cell cytotoxicity in the presence {alpha}-GalCer in vitro. After adoptive transfer of CD1d-restricted T cells and {alpha}-GalCer to mice engrafted with both C1R-CD1c and C1R-CD1d, a reduction in tumor growth was observed only in CD1d+ masses. In addition, CD1d-restricted T-cell treatment plus {alpha}-GalCer eradicated small C1R-CD1d+ nodules. Immunohistochemical analysis revealed that infiltrating NKT cells were mainly observed in CD1d nodules.

Conclusions: Our results indicate that ex vivo expanded cytotoxic CD1d-restricted T cells and {alpha}-GalCer may represent a new immunotherapeutic tool for treatment of CD1d+ hematologic malignancies.

Key words: lymphoproliferative disorders, natural killer T cells, {alpha}-galactosylceramide, CD1d, CD1d-restricted T cells.