Anti-angiogenetic effects of immune-reconstituted influenza virosomes assembled with parathyroid hormone-related protein derived peptide vaccine.
BACKGROUND
C-IRIV/PTR-4 is a novel anticancer vaccine construct composed of immune-reconstituted influenza virosomes (IRIV) assembled with the PTH-rP derived peptide (PTR)-4, a synthetic CTL epitope with HLA-A(*)02.01 amino acid binding motifs. This peptide is able to generate a human PTH-rP specific CTL response with anti-tumor activity in vitro and in mice.


METHODS
We have investigated the immunological and preventive anti-tumor activity of C-IRIV/PTR-4 compared with the soluble PTR-4 peptide, in HHD mice inoculated with autologous PTH-rP+ tumor cells.


RESULTS
Peptide vaccination with either a soluble and an IRIV formulation showed similar immunological activity and the ability to purge the tumor tissue of tumor cell clones able to produce the target antigen (PTR-rP). The most efficient protection from tumor growth was however observed in animals vaccinated with C-IRIV/PTR-4 in which an additional IRIV related anti-angiogenetic effect was detected in the tumor tissue.


CONCLUSIONS
These results confirm the immunological activity of PTR-4 vaccination and suggest a more efficacious therapeutic potential of C-IRIV/PTR-4 against bone metastases and malignancies like breast, prostate and lung which very often over-express PTH-rP.
Correale
Pierpaolo
P
Department G. Segre of Pharmacology, Medical Oncology Section, Department of Human Pathology and Oncology, University of Siena, Viale Bracci 11, 53100 Siena, Italy.
Del Vecchio
Maria Teresa
MT
Renieri
Tommaso
T
Di Genova
Giuseppa
G
La Placa
Marco
M
Remondo
Cinzia
C
Savellini
Gianni Gori
GG
Terrosi
Chiara
C
Zurbriggen
Rinaldo
R
Amacker
Mario
M
Francini
Guido
G
Cusi
Maria Grazia
MG
D000818:Animals; D019496:Cancer Vaccines / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D044162:Parathyroid Hormone-Related Protein / Q000008:administration & dosage*; D022223:Vaccines, Subunit / Q000627:therapeutic use; D022721:Vaccines, Virosome / Q000494:pharmacology* / Q000627:therapeutic use
D019496:Cancer Vaccines; D044162:Parathyroid Hormone-Related Protein; D022223:Vaccines, Subunit; D022721:Vaccines, Virosome