Antitumor vaccination with HER-2-derived recombinant antigens.
Certain types of malignant tumors overexpress HER-2, a transmembrane glycoprotein of the class I receptor tyrosine kinase erbB family. To develop an effective HER-2 vaccine for the selective immunotherapy of these malignancies, we have genetically engineered fusion proteins containing portions of extra- and intracellular HER-2 domains. Activated dendritic cells (DC) cocultured with these novel antigens (Ag) could induce potent responses of Ag-specific T-cell lines in vitro and a protection against HER-2-expressing tumor in vivo. The protective capabilities of HER-2-derived fusion proteins correlated with the efficiency of their presentation to Ag-specific T-cell hybridomas. The most effective Ag contained GM-CSF, the presence of which facilitated their internalization by antigen-presenting cells (APC) in a receptor-mediated manner.
Vidovic
Damir
D
Dendreon Corporation, Seattle, WA, USA. dvidovic@dendreon.com
Graddis
Thomas
T
Chen
Feng
F
Slagle
Paul
P
Diegel
Michael
M
Stepan
Lara
L
Laus
Reiner
R
D000595:Amino Acid Sequence; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000628:therapy*; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology*; D015202:Protein Engineering; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*
D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic