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

Vaccines

Shigetaka Shimodaira⁴  Kenji Sano¹  Koichi Hirabayashi⁴  Terutsugu Koya⁴  Yumiko Higuchi⁴  Yumiko Mizuno⁴  Naoko Yamaoka⁴  Miki Yuzawa⁴  Takashi Kobayashi³  Kenichi Ito²  Tomonobu Koizumi³ 

[1] Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto 8621, Japan; E-Mail:;Department of Breast and Endocrine Surgery, Shinshu University Hospital, Matsumoto 8621, Japan; E-Mail:;Shinshu Cancer Center, Shinshu University Hospital, Matsumoto 8621, Japan; E-Mails:;Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto 8621, Japan; E-Mails:

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

DOI  :  10.3390/vaccines3041004

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.