Abstract
The homeobox protein, PEPP2 (RHOXF2), has been suggested as a cancer/testis (CT) antigen based on its expression pattern. However, the peptide epitope of PEPP2 that is recognized by cytotoxic T cells (CTLs) is unknown. In this study, we revealed that PEPP2 gene was highly expressed in myeloid leukemia cells and some other hematological malignancies. This gene was also expressed in leukemic stem-like cells. We next identified the first reported epitope peptide (PEPP2271-279). The CTLs induced by PEPP2271-279 recognized PEPP2-positive target cells in an HLA-A*24:02-restricted manner. We also found that a demethylating agent, 5-aza-2’-deoxycytidine, could enhance PEPP2 expression in leukemia cells but not in blood mononuclear cells from healthy donors. The cytotoxic activity of anti-PEPP2 CTL against leukemic cells treated with 5-aza-2’-deoxycytidine was higher than that directed against untreated cells. These results suggest a clinical rationale that combined treatment with this novel antigen-specific immunotherapy together with demethylating agents might be effective in therapy-resistant myeloid leukemia patients.
Highlights
The development of chemotherapy regimens and targeted therapies has improved the survival of patients with leukemia
We evaluated PEPP2 gene expression in various types of cancer cell lines by quantitative RT-PCR (Fig 1A and 1B)
The expression of PEPP2 was not observed in other types of cancer cell lines including U87MG, T98G, A147, LU99, EBC1, A549, PK59, PK1, PK8, KU7, JCA1, HSS78, MDA231, and 501Amel
Summary
The development of chemotherapy regimens and targeted therapies has improved the survival of patients with leukemia. This disease continues to recur following conventional therapies in some patients, leading to poor prognosis [1,2]. Eradication of residual disease by additional treatment is necessary for these therapy-resistant patients. By this rationale, immunotherapy using antigen expressed by leukemic cells might be an attractive strategy to cure leukemia patients [3,4,5].
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