An efficient strategy to induce and maintain in vitro human T cells specific for autologous Non-Small Cell Lung Carcinoma

Glenda Canderan, Paola Gruarin, Daniela Montagna, Raffaella Fontana, Giulio Melloni, Catia Traversari, Paolo Dellabona, Giulia Casorati

Research output: Contribution to journalArticle

Abstract

Background: The efficient expansion in vitro of cytolytic CD8+ T cells (CTLs) specific for autologous tumors is crucial both for basic and translational aspects of tumor immunology. We investigated strategies to generate CTLs specific for autologous Non-Small Cell Lung Carcinoma (NSCLC), the most frequent tumor in mankind, using circulating lymphocytes. Principal Findings: Classic Mixed Lymphocyte Tumor Cultures with NSCLC cells consistently failed to induce tumor-specific CTLs. Cross-presentation in vitro of irradiated NSCLC cells by autologous dendritic cells, by contrast, induced specific CTL lines from which we obtained a high number of tumor-specific T cell clones (TCCs). The TCCs displayed a limited TCR diversity, suggesting an origin from few tumor-specific T cell precursors, while their TCR molecular fingerprints were detected in the patient's tumor infiltrating lymphocytes, implying a role in the spontaneous anti-tumor response. Grafting NSCLC-specific TCR into primary allogeneic T cells by lentiviral vectors expressing human V-mouse C chimeric TCRa/b chains overcame the growth limits of these TCCs. The resulting, rapidly expanding CD4+ and CD8+ T cell lines stably expressed the grafted chimeric TCR and specifically recognized the original NSCLC. Conclusions: This study defines a strategy to efficiently induce and propagate in vitro T cells specific for NSCLC starting from autologous peripheral blood lymphocytes.

Original languageEnglish
Article numbere12014
JournalPLoS One
Volume5
Issue number8
DOIs
Publication statusPublished - 2010

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T-cells
Non-Small Cell Lung Carcinoma
carcinoma
T-lymphocytes
lungs
Cells
Tumors
T-Lymphocytes
neoplasms
Lymphocytes
cells
Neoplasms
lymphocytes
Clone Cells
clones
In Vitro Techniques
Cross-Priming
T-Lymphoid Precursor Cells
cell lines
Tumor-Infiltrating Lymphocytes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

An efficient strategy to induce and maintain in vitro human T cells specific for autologous Non-Small Cell Lung Carcinoma. / Canderan, Glenda; Gruarin, Paola; Montagna, Daniela; Fontana, Raffaella; Melloni, Giulio; Traversari, Catia; Dellabona, Paolo; Casorati, Giulia.

In: PLoS One, Vol. 5, No. 8, e12014, 2010.

Research output: Contribution to journalArticle

Canderan, Glenda ; Gruarin, Paola ; Montagna, Daniela ; Fontana, Raffaella ; Melloni, Giulio ; Traversari, Catia ; Dellabona, Paolo ; Casorati, Giulia. / An efficient strategy to induce and maintain in vitro human T cells specific for autologous Non-Small Cell Lung Carcinoma. In: PLoS One. 2010 ; Vol. 5, No. 8.
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AU - Melloni, Giulio

AU - Traversari, Catia

AU - Dellabona, Paolo

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