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Vaccines (Basel). 2015 Dec 11;3(4):1004-18. doi: 10.3390/vaccines3041004.

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

Author information

1
Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto 8621, Japan. shimodai@shinshu-u.ac.jp.
2
Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto 8621, Japan. kenjisa@shinshu-u.ac.jp.
3
Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto 8621, Japan. kohira@shinshu-u.ac.jp.
4
Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto 8621, Japan. koya@shinshu-u.ac.jp.
5
Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto 8621, Japan. sasa0922@shinshu-u.ac.jp.
6
Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto 8621, Japan. purimeron@shinshu-u.ac.jp.
7
Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto 8621, Japan. naoko4152@shinshu-u.ac.jp.
8
Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto 8621, Japan. m1k1yz@shinshu-u.ac.jp.
9
Shinshu Cancer Center, Shinshu University Hospital, Matsumoto 8621, Japan. takob@shinshu-u.ac.jp.
10
Department of Breast and Endocrine Surgery, Shinshu University Hospital, Matsumoto 8621, Japan. kenito@shinshu-u.ac.jp.
11
Shinshu Cancer Center, Shinshu University Hospital, Matsumoto 8621, Japan. tomonobu@shinshu-u.ac.jp.

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.

KEYWORDS:

Wilms’ tumor 1; colorectal cancer; dendritic cell vaccines; enzyme-linked immunosorbent spot assay; immunohistochemistry; tetramer analysis

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