Development and therapeutic effect of adoptively transferred T cells primed by tumor lysate-pulsed autologous dendritic cells in a patient with metastatic endometrial cancer

We describe a 65-year-old woman with a large surgically unresectable and ch emoresistant liver metastasis of endometrial carcinoma who was treated by i nfusion with peripheral blood T cells stimulated with tumor lysate-pulsed a utologous dendritic cells (DC). Extensive in vitro characterization of the DC-activated T cells included phenotypic analysis, cytotoxicity, and intrac ellular cytokine secretion. High cytotoxicity was observed against autologo us tumor cells, but not against NK-sensitive K562 cells, autologous Con-A l ymphoblasts, or autologous Epstein-Barr virus-transformed lymphoblastoid ce lls. Blocking studies demonstrated that lyric activity was HLA class I rest ricted. Two-color flow cytometric analysis revealed that a significant prop ortion of CD8+ T cells was also CD56+, and analysis of intracellular IFN-ga mma and IL-4 expression suggested a type 1 cytokine bias. The patient was t reated by three infusions of tumor-specific T cells at 3- to 4-week interva ls, and in vivo distribution of the T cells was followed by In-111 oxine la beling and serial gamma camera imaging. Tumor localization and accumulation of labeled lymphocytes was consistently detected at serial time points fol lowing each injection. However, deep infiltration of the large tumor mass b y activated T cells was minimal, as evaluated in 3 dimensions by single pho ton emission computerized tomography (SPECT) imaging. Transient serum incre ases of the tumor marker lactate dehydrogenase (LDH), were detectable after each injection. Similar posttreatment elevations were seen for serum uric acid and potassium. Clinically, stabilization of the large liver metastasis was obtained during treatment. Collectively, these results indicate that t umor-specific CD8+ cytotoxic T-cell responses can be generated in patients with endometrial cancer, and suggest that T-cell immunotherapy may be of th erapeutic value in patients harboring metastatic disease. Copyright (C) 200 0 S. Karger AG. Basel.