Tumor immunotherapy with alternative reading frame peptide antigens.
The translation machinery of a eukaryotic cell produces errors in decoding mRNA that may give rise to alternative reading frame (Arf) polypeptides. We predicted these putative aberrant translation products from the cDNA of three tumor-associated antigens (Ag): a transmembrane glycoprotein of the class I receptor tyrosine kinase erbB family HER-2, telomerase reverse transcriptase (TERT) and prostatic acid phosphatase (PAP). Immunization of mice with Arf peptide-pulsed antigen presenting cells (APC) generated potent in vivo immune protection against tumors expressing respective tumor-associated Ag. CD8+ T cells from mice immunized with HER-2 derived protective Arf peptides specifically recognized HER-2 transfected tumor cells. The strategy described here has potential for designing highly efficient novel vaccines for Ag-specific immunotherapy of human malignancies.
Graddis
Thomas J
TJ
Dendreon Corporation, 3005 1st Avenue, Seattle, WA 98121, USA. damir_vidovic@comcast.net
Diegel
Michael L
ML
McMahan
Catherine J
CJ
Tsavler
Larisa
L
Laus
Reiner
R
Vidovic
Damir
D
D000818:Animals; D000941:Antigens / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D004268:DNA-Binding Proteins; D005260:Female; D007167:Immunotherapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D000073718:Pancreatitis-Associated Proteins; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D011506:Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D016364:Reading Frames; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D019098:Telomerase / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D000941:Antigens; D004268:DNA-Binding Proteins; D000073718:Pancreatitis-Associated Proteins; D010446:Peptide Fragments; D011506:Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D019098:Telomerase; C490253:Reg3b protein, mouse; C509186:TERT protein, human; C509187:Tert protein, mouse