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.