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Vaccines 2015, 3(4), 1004-1018; doi:10.3390/vaccines3041004

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

1
Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto 8621, Japan
2
Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto 8621, Japan
3
Shinshu Cancer Center, Shinshu University Hospital, Matsumoto 8621, Japan
4
Department of Breast and Endocrine Surgery, Shinshu University Hospital, Matsumoto 8621, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Diane M. Harper
Received: 30 September 2015 / Revised: 19 November 2015 / Accepted: 7 December 2015 / Published: 11 December 2015
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Abstract

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. View Full-Text
Keywords: dendritic cell vaccines; colorectal cancer; Wilms’ tumor 1; immunohistochemistry; tetramer analysis; enzyme-linked immunosorbent spot assay dendritic cell vaccines; colorectal cancer; Wilms’ tumor 1; immunohistochemistry; tetramer analysis; enzyme-linked immunosorbent spot assay
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Shimodaira, S.; Sano, K.; Hirabayashi, K.; Koya, T.; Higuchi, Y.; Mizuno, Y.; Yamaoka, N.; Yuzawa, M.; Kobayashi, T.; Ito, K.; Koizumi, T. Dendritic Cell-Based Adjuvant Vaccination Targeting Wilms’ Tumor 1 in Patients with Advanced Colorectal Cancer. Vaccines 2015, 3, 1004-1018.

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