New Strategy of Adult T-cell Leukemia Treatment Targeted for Anti-tumor Immunity and a Longevity Gene-encoded Protein

Adult T-cell leukemia-lymphoma (ATL) is an aggressive peripheral T-cell neoplasm with a poor prognosis, developing after long-term infection with human T-cell leukemia virus-1 (HTLV-1). Multiple factors (e.g., virus, host cells, epigenetic aberrations, and immune factors) have been implicated in the development of ATL, although the underlying mechanisms of leukemogenesis have not been fully elucidated. Despite recent progress in both chemotherapy and supportive care for hematological malignancies, the prognosis of ATL is still poor; overall survival at 3 years is only 24 %. New strategies for the therapy and prophylaxis of ATL (e.g., vaccines and novel molecular target agents) are still required. This article reviews new strategy of ATL treatment targeted for HTLV-1-specific cytotoxic T-lymphocytes (CTLs) and SIRT1, a longevity gene-encoded protein. HTLV-1-specific CTLs play a critical role in the host immune response against HTLV-1. We have described here the decreased frequency and function of HTLV-1-specific CD8+ T cells in ATL patients and the efficient induction of the HTLV-1-specific CTLs response in human leukocyte antigen-A* 0201-transgenic mice by the HTLV-1/hepatitis B core chimeric particle and oligomannose-coated liposomes encapsulating HTLV-1 epitope without adjuvant, suggesting that the efficient antigen delivery system and CTL induction can be exploited to develop a prophylactic vaccine model against tumors and infectious diseases. Furthermore, our studies suggest that SIRT1, a longevity gene-encoded protein, is a crucial anti-apoptotic molecule in ATL cells, and that SIRT1 inhibitors may be useful therapeutic agents for leukemia, especially in patients with ATL. These studies targeted for antitumor immunity such as vaccine and SIRT1 may support the new prophylactic and therapeutic approach for ATL.