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


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.
Bagnara
Davide
D
Human Anatomy Section, Department of Experimental Medicine, University of Genoa, Genoa, Italy.
Ibatici
Adalberto
A
Corselli
Mirko
M
Sessarego
Nadia
N
Tenca
Claudya
C
De Santanna
Amleto
A
Mazzarello
Andrea
A
Daga
Antonio
A
Corvò
Renzo
R
De Rossi
Giulio
G
Frassoni
Francesco
F
Ciccone
Ermanno
E
Fais
Franco
F
D000818:Animals; D055610:Antigens, CD1d / Q000378:metabolism*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007107:Immune System; D007150:Immunohistochemistry / Q000379:methods; D007167:Immunotherapy / Q000379:methods; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007694:Killer Cells, Natural / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D009368:Neoplasm Transplantation; D013601:T-Lymphocytes / Q000473:pathology*
D055610:Antigens, CD1d