A novel unconventional antigen MPD5 elicits anti-tumor humoral immune responses in a subset of patients with polycythemia vera.

Overview

In an effort to define the antigenic mechanism that contributes to beneficial therapeutic outcome in patients with polycythemia vera (PV), we screened a human testis cDNA library with serological cloning derived from sera of three PV patients who had undergone therapeutic-induced remission. As a result, we identified a novel antigen, MPD5, which belongs to the group of cryptic antigens with unconventional genomic intron/exon structure. Moreover, MPD5 elicited IgG antibody responses in a subset of PV patients who had benefited from a variety of therapies--including IFN-alpha, Hydroxyurea, Imatinib mesylate, Anagrelide, and phlebotomy--but not in untreated PV patients or healthy donors, suggesting that MPD5 is a PV-associated, therapy-related antigen. In the granulocytes of PV patients who are responsive to therapy, upregulated MPD5 expression may serve to enhance immune responses. These findings provide new insight into the mechanism underlying regulation of the self-antigen repertoire that elicits anti-tumor immune responses in patients with myeloproliferative diseases, indicating the potential of these self-antigens as targets of novel immunotherapy.