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PLoS One. 2010 Aug 9;5(8):e12014. doi: 10.1371/journal.pone.0012014.

An efficient strategy to induce and maintain in vitro human T cells specific for autologous non-small cell lung carcinoma.

Author information

1
Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.

Erratum in

  • PLoS One. 2011;6(1).doi: 10.1371/annotation/df559170-4836-4bc7-a16d-44c7c6339cda. Campi, Gabriele [added].

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 TCRalpha/beta 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.

PMID:
20711505
PMCID:
PMC2918513
DOI:
10.1371/journal.pone.0012014
[Indexed for MEDLINE]
Free PMC Article

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