Predictive biomarkers and effectiveness of MUC1-targeted dendritic-cell-based vaccine in patients with refractory non-small cell lung cancer.
BACKGROUND
The dendritic cell (DC)-based vaccine targeting the highly immunogenic tumor antigen, MUC1, has been promising for a cancer immunotherapy; however, predictive biomarkers for beneficial clinical responses of the vaccine remain to be determined.


METHODS
DCs loaded with MUC1-derived peptide were subcutaneously administered to patients with MUC1-positive non-small cell lung cancer (NSCLC) that was refractory to standard anticancer therapies, every 2 weeks. The effectiveness and tolerability of the vaccine were evaluated, and predictive biomarkers of clinical responses were explored.


RESULTS
Between August 2005 and May 2015, 40 patients received the vaccines. The median survival time (MST) after the initial vaccination was 7.4 months, and the 1-year survival rate was 25.0%. The MST for patients who received more than six vaccinations was 9.5 months, and the 1-year survival rate was 39.3%. In this cohort, patients who experienced immune-related adverse events, including skin reactions at the vaccination site and fever, had significantly longer survival times compared with patients without those immune-related adverse events (12.6versus6.7 months,p= 0.042). Longer survival times were also observed in patients whose peripheral white blood cells contained >20.0% lymphocytes (12.6versus4.5 months;p= 0.014). MUC1-specific cytotoxic immune responses were achieved in all of seven patients analyzed who received six vaccinations.


CONCLUSIONS
The MUC1-targeted DC-based vaccine induced an antitumor immune response that promoted prolonged survival of patients with refractory NSCLC. The occurrence of immune-related adverse events and having a higher percentage of peripheral lymphocytes were predictive biomarkers of a beneficial clinical response during cancer immunotherapy for NSCLC.
Department of Medical Oncology and Surgery, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga 520-2192, Japan.
Koji
K
Teramoto
Department of Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan.
Yoshitomo
Y
Ozaki
Department of Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan.
Jun
J
Hanaoka
Departments of Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan.
Satoru
S
Sawai
Department of Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan.
Noriaki
N
Tezuka
Department of Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan.
Shozo
S
Fujino
Department of Medical Oncology, Shiga University of Medical Science, Otsu, Shiga, Japan.
Yataro
Y
Daigo
Department of Respiratory, Breast and Endocrine Surgery, Kagawa University Faculty of Medicine, Kita-gun, Kagawa, Japan.
Keiichi
K
Kontani
MUC1 tumor antigen; cancer immunotherapy; dendritic-cell-based vaccine; non-small cell lung cancer; predictive biomarker