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

Davide Bagnara, Adalberto Ibatici, Mirko Corselli, Nadia Sessarego, Claudya Tenca, Amleto De Santanna, Andrea Mazzarello, Antonio Daga, Renzo Corvò, Giulio De Rossi, Francesco Frassoni, Ermanno Ciccone, Franco Fais

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: CD1d is a monomorphic antigen presentation molecule expressed in several hematologic malignancies. Alpha- (α-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 α-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 α-GalCer in vitro. After adoptive transfer of CD1d-restricted T cells and α-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 α-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 α-GalCer may represent a new immunotherapeutic tool for treatment of CD1d+ hematologic malignancies.

Original languageEnglish
Pages (from-to)967-974
Number of pages8
JournalHaematologica
Volume94
Issue number7
DOIs
Publication statusPublished - Jul 2009

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Adoptive Immunotherapy
Natural Killer T-Cells
T-Lymphocytes
Neoplasms
Hematologic Neoplasms
Cell Line
CD1d Antigen
Firefly Luciferases
Inbred NOD Mouse
SCID Mice
Adoptive Transfer
Glycolipids
Antigen Presentation
Growth
Immunotherapy
Theoretical Models
Therapeutics
Lymphocytes
Infection

Keywords

  • α- galactosylceramide
  • CD1d
  • CD1d-restricted T cells
  • Lymphoproliferative disorders
  • Natural killer T cells

ASJC Scopus subject areas

  • Hematology

Cite this

Adoptive immunotherapy mediated by ex vivo expanded natural killer T cells against CD1d-expressing lymphoid neoplasms. / Bagnara, Davide; Ibatici, Adalberto; Corselli, Mirko; Sessarego, Nadia; Tenca, Claudya; De Santanna, Amleto; Mazzarello, Andrea; Daga, Antonio; Corvò, Renzo; De Rossi, Giulio; Frassoni, Francesco; Ciccone, Ermanno; Fais, Franco.

In: Haematologica, Vol. 94, No. 7, 07.2009, p. 967-974.

Research output: Contribution to journalArticle

Bagnara, D, Ibatici, A, Corselli, M, Sessarego, N, Tenca, C, De Santanna, A, Mazzarello, A, Daga, A, Corvò, R, De Rossi, G, Frassoni, F, Ciccone, E & Fais, F 2009, 'Adoptive immunotherapy mediated by ex vivo expanded natural killer T cells against CD1d-expressing lymphoid neoplasms', Haematologica, vol. 94, no. 7, pp. 967-974. https://doi.org/10.3324/haematol.2008.001339
Bagnara, Davide ; Ibatici, Adalberto ; Corselli, Mirko ; Sessarego, Nadia ; Tenca, Claudya ; De Santanna, Amleto ; Mazzarello, Andrea ; Daga, Antonio ; Corvò, Renzo ; De Rossi, Giulio ; Frassoni, Francesco ; Ciccone, Ermanno ; Fais, Franco. / Adoptive immunotherapy mediated by ex vivo expanded natural killer T cells against CD1d-expressing lymphoid neoplasms. In: Haematologica. 2009 ; Vol. 94, No. 7. pp. 967-974.
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abstract = "Background: CD1d is a monomorphic antigen presentation molecule expressed in several hematologic malignancies. Alpha- (α-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 α-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 α-GalCer in vitro. After adoptive transfer of CD1d-restricted T cells and α-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 α-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 α-GalCer may represent a new immunotherapeutic tool for treatment of CD1d+ hematologic malignancies.",
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AU - Ibatici, Adalberto

AU - Corselli, Mirko

AU - Sessarego, Nadia

AU - Tenca, Claudya

AU - De Santanna, Amleto

AU - Mazzarello, Andrea

AU - Daga, Antonio

AU - Corvò, Renzo

AU - De Rossi, Giulio

AU - Frassoni, Francesco

AU - Ciccone, Ermanno

AU - Fais, Franco

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N2 - Background: CD1d is a monomorphic antigen presentation molecule expressed in several hematologic malignancies. Alpha- (α-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 α-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 α-GalCer in vitro. After adoptive transfer of CD1d-restricted T cells and α-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 α-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 α-GalCer may represent a new immunotherapeutic tool for treatment of CD1d+ hematologic malignancies.

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