Tumour-associated antigen (TAA)-specific cytotoxic T cell (CTL) response in vitro and in a mouse model, induced by TAA-plasmids delivered by influenza virosomes

We investigated influenza virosomes as a TAA-gene delivery system for use i n TAA-directed anti-cancer vaccine therapy. An engineered plasmid (GC90) ex pressing the parathyroid hormone-related peptide (PTH-rP), a protein secret ed by prostate and lung carcinoma cells, was included in influenza virosome s (GC90V). The ability of GC90V to elicit a PTH-rP-specific cytotoxic T cel l (CTL) response was demonstrated in BALB/c mice immunised with intranasal (i.n.) GC90V +/- adjuvant subcutaneous (s.c.) interleukin-2 (IL-2). A PTH-r P-specific CTL response with antitumour activity was also demonstrated in h uman peripheral blood mononuclear cells (PBMC) stimulated in vitro with GC9 0V infected autologous dendritic cells (DC). These results provide a ration ale for investigating GC90V in clinical trials of anticancer vaccine therap y. (C) 2001 Elsevier Science Ltd. All rights reserved.