title: Clinical outcomes of a novel therapeutic vaccine with Tax peptide-pulsed dendritic cells for adult T cell leukaemia/lymphoma in a pilot study.
abstract: Adult T cell leukaemia/lymphoma (ATL) is a human T cell leukaemia virus type-I (HTLV-I)-infected T cell malignancy with poor prognosis. We herein developed a novel therapeutic vaccine designed to augment an HTLV-I Tax-specific cytotoxic T lymphocyte (CTL) response that has been implicated in anti-ATL effects, and conducted a pilot study to investigate its safety and efficacy. Three previously treated ATL patients, classified as intermediate- to high-risk, were subcutaneously administered with the vaccine, consisting of autologous dendritic cells (DCs) pulsed with Tax peptides corresponding to the CTL epitopes. In all patients, the performance status improved after vaccination without severe adverse events, and Tax-specific CTL responses were observed with peaks at 16-20 weeks. Two patients achieved partial remission in the first 8 weeks, one of whom later achieved complete remission, maintaining their remission status without any additional chemotherapy 24 and 19 months after vaccination, respectively. The third patient, whose tumour cells lacked the ability to express Tax at biopsy, obtained stable disease in the first 8 weeks and later developed slowly progressive disease although additional therapy was not required for 14 months. The clinical outcomes of this pilot study indicate that the Tax peptide-pulsed DC vaccine is a safe and promising immunotherapy for ATL.
authors.affiliation: Department of Haematology, National Kyushu Cancer Centre, Fukuoka, Japan.
authors.forename: Youko
authors.initials: Y
authors.lastname: Suehiro
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Hasegawa
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Iino
authors.forename: Amane
authors.initials: A
authors.lastname: Sasada
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Watanabe
authors.forename: Masao
authors.initials: M
authors.lastname: Matsuoka
authors.forename: Ayako
authors.initials: A
authors.lastname: Takamori
authors.forename: Ryuji
authors.initials: R
authors.lastname: Tanosaki
authors.forename: Atae
authors.initials: A
authors.lastname: Utsunomiya
authors.forename: Ilseung
authors.initials: I
authors.lastname: Choi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fukuda
authors.forename: Osamu
authors.initials: O
authors.lastname: Miura
authors.forename: Shigeo
authors.initials: S
authors.lastname: Takaishi
authors.forename: Takanori
authors.initials: T
authors.lastname: Teshima
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
authors.forename: Mari
authors.initials: M
authors.lastname: Kannagi
authors.forename: Naokuni
authors.initials: N
authors.lastname: Uike
authors.forename: Jun
authors.initials: J
authors.lastname: Okamura
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D016356:Gene Products, tax / Q000737:chemistry / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics; D006801:Humans; D007167:Immunotherapy; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology*; D010865:Pilot Projects; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines; D016356:Gene Products, tax; D010446:Peptide Fragments
keywords: adult T cell leukaemia/lymphoma; cytotoxic T lymphocyte; dendritic cell; human T cell leukaemia virus type-I; tumour vaccine