title: An efficient strategy to induce and maintain in vitro human T cells specific for autologous non-small cell lung carcinoma.
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.
  
  
  RESULTS
  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.
authors: Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
authors: Glenda
authors: G
authors: Canderan
authors: Paola
authors: P
authors: Gruarin
authors: Daniela
authors: D
authors: Montagna
authors: Raffaella
authors: R
authors: Fontana
authors: Gabriele
authors: G
authors: Campi
authors: Giulio
authors: G
authors: Melloni
authors: Catia
authors: C
authors: Traversari
authors: Paolo
authors: P
authors: Dellabona
authors: Giulia
authors: G
authors: Casorati
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002999:Clone Cells; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D011948:Receptors, Antigen, T-Cell