In vivo study of the GC90/IRIV vaccine for immune response and autoimmunity into a novel humanised transgenic mouse.
Parathyroid hormone-related protein (PTH-rP), a secreted protein produced by prostate carcinoma and other epithelial cancers, is considered a key agent for the development of bone metastases. We investigated the construct GC90/IRIV, composed of immunopotentiating reconstituted influenza virosomes (IRIV) containing PTH-rP gene plasmids (GC90), as a potential tool for human anticancer immunotherapy into humanised mice transgenic for HLA-A(*)02.01, the human-beta2 microglobulin, and the human CD8alpha molecule. Intranasal administration of GC90/IRIV resulted in the induction of a PTH-rP-specific multiepitope cytotoxic T-cell (CTL) response. Cytotoxic T cells derived from vaccinated mice were capable of lysing in vitro syngenic murine PTH-rP transfectants and human HLA-A((*))02.01(+)/PTH-rP(+) prostate carcinoma LNCaP cells as well. The immune response capacity and the absence of any sign of toxicity and/or autoimmunity in vivo suggest the GC90/IRIV vaccine as a valid tool for active specific immunotherapy of human cancers and metastases overexpressing PTH-rP.
Scardino
A
A
INSERM U. 487, IGR, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France. cusi@unisi.it
Correale
P
P
Firat
H
H
Pellegrini
M
M
Kosmatopoulos
K
K
Opolon
P
P
Alves
P
P
Zurbriggen
R
R
Glück
R
R
Lemonnier
F A
FA
Francini
G
G
Cusi
M G
MG
D000818:Animals; D019496:Cancer Vaccines; D002277:Carcinoma / Q000235:genetics / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D036361:Peptide Hormones / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D010957:Plasmids; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D036361:Peptide Hormones