An Efficient Strategy to Induce and Maintain In Vitro Human T Cells Specific for Autologous Non-Small Cell Lung Carcinoma

作者：Canderan Glenda^*; Gruarin Paola; Montagna Daniela; Fontana Raffaella; Melloni Giulio; Traversari Catia; Dellabona Paolo; Casorati Giulia

来源：PLos One, 2010, 5(8): e12014.

DOI：10.1371/journal.pone.0012014

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 TCR alpha/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.

• 出版日期2010-8-9