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 in TAA-directed anti-cancer vaccine therapy. An engineered plasmid (GC90) expressing the parathyroid hormone-related peptide (PTH-rP), a protein secreted by prostate and lung carcinoma cells, was included in influenza virosomes (GC90V). The ability of GC90V to elicit a PTH-rP-specific cytotoxic T cell (CTL) response was demonstrated in BALB/c mice immunised with intranasal (i.n.) GC90V+/-adjuvant subcutaneous (s.c.) interleukin-2 (IL-2). A PTH-rP-specific CTL response with antitumour activity was also demonstrated in human peripheral blood mononuclear cells (PBMC) stimulated in vitro with GC90V infected autologous dendritic cells (DC). These results provide a rationale for investigating GC90V in clinical trials of anticancer vaccine therapy.
Correale
P
P
Medical Oncology Division, Medicine School, Siena University, 53100, Siena, Italy.
Cusi
M G
MG
Sabatino
M
M
Micheli
L
L
Pozzessere
D
D
Nencini
C
C
Valensin
P E
PE
Petrioli
R
R
Giorgi
G
G
Zurbriggen
R
R
Gluck
R
R
Francini
G
G
D000281:Administration, Intranasal; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D018929:Cell Culture Techniques; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D009980:Influenza A virus / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology; D044162:Parathyroid Hormone-Related Protein; D010957:Plasmids; D011506:Proteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection / Q000379:methods; D014407:Tumor Cells, Cultured; D022701:Virosomes
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D009363:Neoplasm Proteins; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D022701:Virosomes