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

• Published in: European journal of cancer (1990) 2013-03, Vol.49 (4), p.852-859
• Main Authors: Takahashi, Hidenori, Okamoto, Masato, Shimodaira, Shigetaka, Tsujitani, Shun-ichi, Nagaya, Masaki, Ishidao, Takefumi, Kishimoto, Junji, Yonemitsu, Yoshikazu
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - immunology; Adenocarcinoma - mortality; Adenocarcinoma - therapy; Adult; Aged; Aged, 80 and over; Biological and medical sciences; 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 cell vaccine; Dendritic Cells - immunology; Dendritic Cells - transplantation; Female; Follow-Up Studies; Hematology, Oncology and Palliative Medicine; Humans; Lung Neoplasms - immunology; Lung Neoplasms - mortality; Lung Neoplasms - therapy; Male; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - immunology; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - therapy; Neoplasm Staging; Non-small cell lung cancer; Overall survival; Peptide Fragments - immunology; Pharmacology. Drug treatments; Prognosis; Retrospective Studies; Survival Rate; T-Lymphocytes, Cytotoxic - immunology; Tumors; Wilms’ tumour-1; WT1 Proteins - immunology
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2012.11.005

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.