Impact of dendritic cell vaccines pulsed with Wilms' tumour-1 peptide antigen on the survival of patients with advanced non-small cell lung cancers

Eur J Cancer. 2013 Mar;49(4):852-9. doi: 10.1016/j.ejca.2012.11.005. Epub 2012 Dec 11.

Abstract

Purpose: Dendritic cell (DC)-based vaccines have been expected to serve as new therapeutic approaches for advanced non-small cell lung cancers (NSCLCs); however, their clinical outcomes have not been fully elucidated. We report a single-centre clinical study analysing factors affecting the survival of patients with advanced NSCLCs who received DC vaccines pulsed with or without Wilms' tumour protein-1 (WT1) peptide.

Methods: Among 62 patients with previously treated inoperable or postoperatively relapsed NSCLCs who met the inclusion criteria, DCs from 47 (76%) patients who showed HLA-A2402/0201/0206 were pulsed with one or more corresponding WT1 peptide antigens. DC vaccines were intradermally injected biweekly.

Results: Clinical responses based on response evaluation criteria in solid tumours (RECIST) were found in 31 (50%) patients at 3 months after the first DC vaccine (complete response: 1 (1.6%), partial response: 4 (6.5%), stable disease: 26 (41.9%)). Median survival time was 27 months (82% in 1 year and 54% in 2 years) from initial diagnosis, and that was 12 months (48% in 1 year and 22% in 2 years) from the first DC vaccination. Importantly, multivariate analyses revealed that only two factors, blood haemoglobin and the use of WT1 peptides, significantly affected the overall survival of patients from both initial diagnosis and first vaccination.

Conclusions: This study is the first to suggest that DC vaccines pulsed with WT1 may hold a significant impact to prolong the overall survival of patients with advanced NSCLCs.

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / mortality
  • Adenocarcinoma / therapy
  • Adult
  • Aged
  • Aged, 80 and over
  • Cancer Vaccines / therapeutic use*
  • Carcinoma, Large Cell / immunology
  • Carcinoma, Large Cell / mortality
  • Carcinoma, Large Cell / therapy
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / therapy
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation*
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / immunology
  • Lung Neoplasms / mortality
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / therapy
  • Neoplasm Staging
  • Peptide Fragments / immunology*
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • T-Lymphocytes, Cytotoxic / immunology
  • WT1 Proteins / immunology*

Substances

  • Cancer Vaccines
  • Peptide Fragments
  • WT1 Proteins