Clinical outcomes of a novel therapeutic vaccine with Tax peptide-pulsed dendritic cells for adult T cell leukaemia/lymphoma in a pilot study

Br J Haematol. 2015 May;169(3):356-67. doi: 10.1111/bjh.13302. Epub 2015 Jan 22.

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.

Keywords: adult T cell leukaemia/lymphoma; cytotoxic T lymphocyte; dendritic cell; human T cell leukaemia virus type-I; tumour vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology*
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Female
  • Gene Products, tax / chemistry
  • Gene Products, tax / immunology*
  • Human T-lymphotropic virus 1 / genetics
  • Humans
  • Immunotherapy
  • Leukemia-Lymphoma, Adult T-Cell / diagnosis
  • Leukemia-Lymphoma, Adult T-Cell / immunology*
  • Leukemia-Lymphoma, Adult T-Cell / therapy*
  • Male
  • Middle Aged
  • Peptide Fragments / immunology*
  • Pilot Projects
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Cancer Vaccines
  • Cytokines
  • Gene Products, tax
  • Peptide Fragments