UNCONVENTIONAL ANTIGEN TRANSLATED BY A NOVEL INTERNAL RIBOSOME ENTRY SITE ELICITS ANTITUMOR HUMORAL IMMUNE REACTIONS

摘要

The invention provides a novel antigen, MPD6, which belongs to the group of cryptic antigens without conventional genomic structure and is encoded by a cryptic open reading frame located in the 3′ untranslated region (3′UTR) of myotrophin mRNA. MPD6 elicits IgG antibody responses in a subset of PV patients, as well as patients with chronic myelogenous leukemia and prostate cancer. The translation of MPD6 was mediated by a novel internal ribosome entry site (IRES) upstream of the MPD6 reading frame. Furthermore, the MPD6-IRES mediated translation, but not myotrophin-MPD6 transcription, was significantly upregulated in response to IFN-α stimulation. These findings demonstrate that a novel IRES-mediated mechanism is responsible for the translation of unconventional self-antigen MPD6 in responsive to IFN-α stimulation. The eliciting anti-tumor immune response against unconventional antigen MPD6 in patients with myeloproliferative diseases indicates MPD6 as a target of novel immunotherapy.