Media type: E-Article Title: Presentation of native TROP‐2 tumor antigens to human cytotoxic T lymphocytes by engineered antigen‐presenting cells Contributor: Mangino, Giorgio; Grazia Capri, Maria; Barnaba, Vincenzo; Alberti, Saverio imprint: Wiley, 2002 Published in: International Journal of Cancer Language: English DOI: 10.1002/ijc.10616 ISSN: 0020-7136; 1097-0215 Keywords: Cancer Research ; Oncology Origination: Footnote: Description: <jats:title>Abstract</jats:title><jats:p>Professional antigen‐presenting cells (APC), <jats:italic>e.g.</jats:italic> dendritic cells, express immuno‐proteasome components and process proteins for MHC presentation differently from non‐immune cells. Thus, they induce reactivities against sets of peptides that do not overlap with those generated by non‐professional APC, <jats:italic>i.e.</jats:italic>, tumor cells, and stimulate cytotoxic T lymphocytes (CTL) that may not recognize them. The goal of this work was to establish a system for antigen presentation and <jats:italic>in vitro</jats:italic> stimulation of human CTL using “tumor‐cell‐like” engineered APC. Murine fibroblasts were transfected with human <jats:italic>HLA</jats:italic> Class I alleles, together with the <jats:italic>B7.1</jats:italic>, <jats:italic>ICAM‐1</jats:italic> and germ‐line <jats:italic>TROP2</jats:italic> genes. The last encodes a cell surface glycoprotein widely expressed by human cancers. Unseparated peripheral blood mononuclear cells from HLA Class I‐matched individuals were stimulated <jats:italic>in vitro</jats:italic> by the engineered APC. These efficiently induced the activation and proliferation of antigen‐specific HLA‐restricted CTL lines and clones. The Trop‐2‐specific CTL demonstrated high specific cytotoxicity against the appropriate transfected target cells. They also efficiently lysed MCF‐7 human tumor cells expressing endogenous HLA‐A2.1, Trop‐2 together with ICAM‐1. These results demonstrate that Trop‐2 is a target molecule recognized by human CTL. Moreover, they demonstrate that non‐immune engineered APC efficiently process and present native tumor‐specific proteins in the context of human MHC Class I, and stimulate the growth and cytotoxicity of specific anti‐tumor CTL. © 2002 Wiley‐Liss, Inc.</jats:p> Access State: Open Access