title: HTLV-1-targeted immunotherapy.
abstract: Adult T-cell leukemia/lymphoma (ATL) is a HTLV-1 induced T-cell malignancy with an extremely poor prognosis. There is a long latency period between HTLV-1 infection and the onset of ATL, which indicates the existence of multistep mechanisms of leukemogenesis in the infected cells. Tax, which is encoded by the HTLV-1 pX region, plays a crucial role in HTLV-1 leukemogenesis and is a major target of CTL. We developed an anti-ATL therapeutic vaccine consisting of autologous dendritic cells that is pulsed with Tax peptides (Tax-DC). The vaccination protocol was completed with three injections at a 2-week interval, within one month. Good quality of life and long-term treatment-free survival were observed for more than 3 years in two of the three patients enrolled in the pilot study. Furthermore, the proviral load remained mostly around the carrier level, with minor fluctuation, after vaccination. Tax-specific proliferative CTL responses were observed in all cases and sporadically augmented responses were also subsequently detected. The Tax-DC vaccine might be a well-tolerated and long-lasting maintenance therapy that is acceptable even for elderly patients. Based on the encouraging results, we are now conducting a clinical trial of Tax-DC vaccine combined with anti-CCR4 antibody to enhance the efficacy of the vaccine as next-generation immunotherapy.
authors: Department of Hematology, Department of Cell Therapy, National Kyushu Cancer Center.
authors: Youko
authors: Y
authors: Suehiro
mesh_terms: D003713:Dendritic Cells / Q000276:immunology; D015696:Gene Products, tat / Q000235:genetics / Q000276:immunology; D016679:Genome, Viral; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology / Q000628:therapy* / Q000821:virology; D014611:Vaccination
chemical_list: D015696:Gene Products, tat