PMID- 26690485 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20151222 LR - 20201001 IS - 2076-393X (Print) IS - 2076-393X (Electronic) IS - 2076-393X (Linking) VI - 3 IP - 4 DP - 2015 Dec 11 TI - Dendritic Cell-Based Adjuvant Vaccination Targeting Wilms' Tumor 1 in Patients with Advanced Colorectal Cancer. PG - 1004-18 LID - 10.3390/vaccines3041004 [doi] AB - 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 x 10(7) 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-gamma-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. FAU - Shimodaira, Shigetaka AU - Shimodaira S AD - Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto 8621, Japan. shimodai@shinshu-u.ac.jp. FAU - Sano, Kenji AU - Sano K AD - Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto 8621, Japan. kenjisa@shinshu-u.ac.jp. FAU - Hirabayashi, Koichi AU - Hirabayashi K AD - Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto 8621, Japan. kohira@shinshu-u.ac.jp. FAU - Koya, Terutsugu AU - Koya T AD - Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto 8621, Japan. koya@shinshu-u.ac.jp. FAU - Higuchi, Yumiko AU - Higuchi Y AD - Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto 8621, Japan. sasa0922@shinshu-u.ac.jp. FAU - Mizuno, Yumiko AU - Mizuno Y AD - Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto 8621, Japan. purimeron@shinshu-u.ac.jp. FAU - Yamaoka, Naoko AU - Yamaoka N AD - Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto 8621, Japan. naoko4152@shinshu-u.ac.jp. FAU - Yuzawa, Miki AU - Yuzawa M AD - Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto 8621, Japan. m1k1yz@shinshu-u.ac.jp. FAU - Kobayashi, Takashi AU - Kobayashi T AD - Shinshu Cancer Center, Shinshu University Hospital, Matsumoto 8621, Japan. takob@shinshu-u.ac.jp. FAU - Ito, Kenichi AU - Ito K AD - Department of Breast and Endocrine Surgery, Shinshu University Hospital, Matsumoto 8621, Japan. kenito@shinshu-u.ac.jp. FAU - Koizumi, Tomonobu AU - Koizumi T AD - Shinshu Cancer Center, Shinshu University Hospital, Matsumoto 8621, Japan. tomonobu@shinshu-u.ac.jp. LA - eng PT - Journal Article DEP - 20151211 PL - Switzerland TA - Vaccines (Basel) JT - Vaccines JID - 101629355 PMC - PMC4693229 OTO - NOTNLM OT - Wilms' tumor 1 OT - colorectal cancer OT - dendritic cell vaccines OT - enzyme-linked immunosorbent spot assay OT - immunohistochemistry OT - tetramer analysis EDAT- 2015/12/23 06:00 MHDA- 2015/12/23 06:01 PMCR- 2015/12/11 CRDT- 2015/12/23 06:00 PHST- 2015/09/30 00:00 [received] PHST- 2015/11/19 00:00 [revised] PHST- 2015/12/07 00:00 [accepted] PHST- 2015/12/23 06:00 [entrez] PHST- 2015/12/23 06:00 [pubmed] PHST- 2015/12/23 06:01 [medline] PHST- 2015/12/11 00:00 [pmc-release] AID - vaccines3041004 [pii] AID - vaccines-03-01004 [pii] AID - 10.3390/vaccines3041004 [doi] PST - epublish SO - Vaccines (Basel). 2015 Dec 11;3(4):1004-18. doi: 10.3390/vaccines3041004.