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Abstract
PURPOSE: The purpose of this study was to determined if tumor-infiltrating lymphocytes (TIL) isolated from transgenic intraocular tumors were capable of preventing the development of spontaneous hepatic metastases. METHODS: Tumor-infiltrating lymphocytes were isolated from intraocular tumors in immunocompetent mice and were examined for cytolytic activity in vitro. The antigenic phenotypes of the TIL were determined by in situ immunohistology. Cultured TIL were transferred adoptively to immunoincompetent, intraocular, tumor-bearing recipients to determine the efficacy of TIL in preventing spontaneous liver metastases. RESULTS: Cultured TIL displayed remarkable cytolytic activity in vitro and antimetastatic properties after adoptive transfer into immunoincompetent, athymic nude mice and anti-CD4/CD8-treated euthymic FVB/N mice. Hepatic metastases developed in only 2 of 10 athymic nude mice that subsequently received TIL, whereas metastases developed in all 10 control mice. Similar results were found in anti-CD4/CD8-treated FVB/N mice. Hepatic metastases did not develop in any of the 10 mice treated with TIL, whereas extensive metastatic foci developed in all 10 untreated FVB/N control mice. The efficacy of TIL therapy was manifested also by significant prolongation of host survival times. CONCLUSIONS: Tumor-infiltrating lymphocytes isolated from intraocular tumors can be expanded in vitro and can exert antimetastatic effects in vivo.