PMID- 34065520 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210615 IS - 2076-393X (Print) IS - 2076-393X (Electronic) IS - 2076-393X (Linking) VI - 9 IP - 5 DP - 2021 May 20 TI - Quality Verification with a Cluster-Controlled Manufacturing System to Generate Monocyte-Derived Dendritic Cells. LID - 10.3390/vaccines9050533 [doi] LID - 533 AB - Dendritic cell (DC) vaccines for cancer immunotherapy have been actively developed to improve clinical efficacy. In our previous report, monocyte-derived DCs induced by interleukin (IL)-4 with a low-adherence dish (low-adherent IL-4-DCs: la-IL-4-DCs) improved the yield and viability, as well as relatively prolonged survival in vitro, compared to IL-4-DCs developed using an adherent culture protocol. However, la-IL-4-DCs exhibit remarkable cluster formation and display heterogeneous immature phenotypes. Therefore, cluster formation in la-IL-4-DCs needs to be optimized for the clinical development of DC vaccines. In this study, we examined the effects of cluster control in the generation of mature IL-4-DCs, using cell culture vessels and measuring spheroid formation, survival, cytokine secretion, and gene expression of IL-4-DCs. Mature IL-4-DCs in cell culture vessels (cluster-controlled IL-4-DCs: cc-IL-4-DCs) displayed increased levels of CD80, CD86, and CD40 compared with that of la-IL-4-DCs. cc-IL-4-DCs induced antigen-specific cytotoxic T lymphocytes (CTLs) with a human leukocyte antigen (HLA)-restricted melanoma antigen recognized by T cells 1 (MART-1) peptide. Additionally, cc-IL-4-DCs produced higher levels of IFN-gamma, possessing the CTL induction. Furthermore, DNA microarrays revealed the upregulation of BCL2A1, a pro-survival gene. According to these findings, the cc-IL-4-DCs are useful for generating homogeneous and functional IL-4-DCs that would be expected to promote long-lasting effects in DC vaccines. FAU - Kawaguchi, Haruhiko AU - Kawaguchi H AD - Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku, Ishikawa 920-0293, Japan. FAU - Sakamoto, Takuya AU - Sakamoto T AUID- ORCID: 0000-0003-2519-4510 AD - Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku, Ishikawa 920-0293, Japan. AD - Center for Regenerative Medicine, Kanazawa Medical University Hospital, Uchinada, Kahoku, Ishikawa 920-0293, Japan. FAU - Koya, Terutsugu AU - Koya T AD - Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku, Ishikawa 920-0293, Japan. AD - Center for Regenerative Medicine, Kanazawa Medical University Hospital, Uchinada, Kahoku, Ishikawa 920-0293, Japan. FAU - Togi, Misa AU - Togi M AUID- ORCID: 0000-0002-7424-4548 AD - Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku, Ishikawa 920-0293, Japan. AD - Center for Regenerative Medicine, Kanazawa Medical University Hospital, Uchinada, Kahoku, Ishikawa 920-0293, Japan. FAU - Date, Ippei AU - Date I AD - Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku, Ishikawa 920-0293, Japan. FAU - Watanabe, Asuka AU - Watanabe A AD - Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku, Ishikawa 920-0293, Japan. FAU - Yoshida, Kenichi AU - Yoshida K AD - Center for Regenerative Medicine, Kanazawa Medical University Hospital, Uchinada, Kahoku, Ishikawa 920-0293, Japan. FAU - Kato, Tomohisa AU - Kato T AD - Medical Research Institute, Kanazawa Medical University, Uchinada, Kahoku, Ishikawa 920-0293, Japan. FAU - Nakamura, Yuka AU - Nakamura Y AD - Medical Research Institute, Kanazawa Medical University, Uchinada, Kahoku, Ishikawa 920-0293, Japan. FAU - Ishigaki, Yasuhito AU - Ishigaki Y AUID- ORCID: 0000-0003-1012-8430 AD - Medical Research Institute, Kanazawa Medical University, Uchinada, Kahoku, Ishikawa 920-0293, Japan. FAU - Shimodaira, Shigetaka AU - Shimodaira S AUID- ORCID: 0000-0002-6612-6912 AD - Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku, Ishikawa 920-0293, Japan. AD - Center for Regenerative Medicine, Kanazawa Medical University Hospital, Uchinada, Kahoku, Ishikawa 920-0293, Japan. LA - eng PT - Journal Article DEP - 20210520 PL - Switzerland TA - Vaccines (Basel) JT - Vaccines JID - 101629355 PMC - PMC8160655 OTO - NOTNLM OT - BCL2A1 OT - cluster control OT - cluster formation OT - dendritic cells OT - immunotherapy OT - vaccine COIS- The authors declare no conflict of interest. EDAT- 2021/06/03 06:00 MHDA- 2021/06/03 06:01 PMCR- 2021/05/20 CRDT- 2021/06/02 01:13 PHST- 2021/04/05 00:00 [received] PHST- 2021/05/14 00:00 [revised] PHST- 2021/05/17 00:00 [accepted] PHST- 2021/06/02 01:13 [entrez] PHST- 2021/06/03 06:00 [pubmed] PHST- 2021/06/03 06:01 [medline] PHST- 2021/05/20 00:00 [pmc-release] AID - vaccines9050533 [pii] AID - vaccines-09-00533 [pii] AID - 10.3390/vaccines9050533 [doi] PST - epublish SO - Vaccines (Basel). 2021 May 20;9(5):533. doi: 10.3390/vaccines9050533.