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

被引：18

作者：

Bagnara, Davide

Ibatici, Adalberto ^{[2
]}

Corselli, Mirko ^{[2
]}

Sessarego, Nadia ^{[2
]}

Tenca, Claudya

De Santanna, Amleto ^{[3
]}

Mazzarello, Andrea

Daga, Antonio ^{[4
]}

Corvo, Renzo ^{[5
]}

De Rossi, Giulio ^{[6
]}

Frassoni, Francesco ^{[2
]}

Ciccone, Ermanno

Fais, Franco ^{[1
]}

机构：

[1] Univ Genoa, Dept Expt Med, Human Anat Sect, I-16132 Genoa, Italy

[2] Osped San Martino Genova, Ctr Cellule Staminali & Terapia Cellulare, Genoa, Italy

[3] Univ Genoa, Dept Expt Med, Histol Sect, I-16132 Genoa, Italy

[4] IST Natl Canc Res Inst, Dept Translat Oncol, Genoa, Italy

[5] IST Natl Canc Res Inst, Dept Otolaryngol, Genoa, Italy

[6] Bambino Gesu Pediat Hosp, Dept Pediat Hematol & Oncol, Rome, Italy

来源：

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL | 2009年 / 94卷 / 07期

关键词：

lymphoproliferative disorders; natural killer T cells; alpha-galactosylceramide; CD1d; CD1d-restricted T cells; ALPHA-GALACTOSYLCERAMIDE KRN7000; NKT CELLS; ANTIGEN PRESENTATION; LEUKEMIA CELLS; TCR ALPHA; PHASE-I; ACTIVATION; CD1D; EXPRESSION; THERAPIES;

D O I：

10.3324/haematol.2008.001339

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：967 / 974

页数：8

共 29 条

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