Dendritic Cell-Based Adjuvant Vaccination Targeting Wilms' Tumor 1 in Patients with Advanced Colorectal Cancer

• Published in: Vaccines (Basel) Vol. 3; no. 4; pp. 1004 - 1018
• Main Authors: Shimodaira, Shigetaka, Sano, Kenji, Hirabayashi, Koichi, Koya, Terutsugu, Higuchi, Yumiko, Mizuno, Yumiko, Yamaoka, Naoko, Yuzawa, Miki, Kobayashi, Takashi, Ito, Kenichi, Koizumi, Tomonobu
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 11.12.2015; MDPI
• Subjects: Colorectal cancer; dendritic cell vaccines; enzyme-linked immunosorbent spot assay; Immunohistochemistry; Kidney cancer; tetramer analysis; Vaccines; Wilms’ tumor 1; colorectal cancer; enzyme-linked immunosorbent spot assay; immunohistochemistry; Wilms’ tumor 1; tetramer analysis; dendritic cell vaccines
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines3041004

Despite significant recent advances in the development of immune checkpoint inhibitors, the treatment of advanced colorectal cancer involving metastasis to distant organs remains challenging. We conducted a phase I study to investigate the safety and immunogenicity of Wilms' tumor (WT1) class I/II peptides-pulsed dendritic cell DC vaccination for patients with advanced colorectal cancer. Standard treatment comprising surgical resection and chemotherapy was followed by one course of seven biweekly administrations of 1-2 × 10⁷ DCs with 1-2 KE of OK-432 (streptococcal preparation) in three patients. Clinical efficacy was confirmed based on WT1 expression using immunohistochemistry on paraffin-embedded tissues and immune monitoring using tetramer analysis and enzyme-linked immunosorbent spot (ELISPOT) assays. WT1 expression with human leukocyte antigen (HLA)-class I molecules was detected in surgical resected tissues. Adverse reactions to DC vaccinations were tolerable under an adjuvant setting. WT1-specific cytotoxic T cells were detected by both modified WT1-peptide/HLA-A*24:02 tetramer analysis and/or interferon-γ-producing cells through the use of ELISPOT assays after the first DC vaccination. Immunity acquired from DC vaccination persisted for two years with prolonged disease-free and overall survival. The present study indicated that DC vaccination targeting WT1 demonstrated the safety and immunogenicity as an adjuvant therapy in patients with resectable advanced colorectal cancer.