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Open AccessArticle

Dendritic Cells Pre-Pulsed with Wilms’ Tumor 1 in Optimized Culture for Cancer Vaccination

1
Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, Kahoku 920-0293, Japan
2
Center for Regenerative medicine, Kanazawa Medical University Hospital, Uchinada, Kahoku 920-0293, Japan
3
Center for Advanced Cell Therapy, Shinshu University Hospital, Matsumoto, Nagano 390-8621, Japan
4
Department of Gastroenterology and Hepatology, The Jikei University School of Medicine, Kashiwa, Chiba 277-8567, Japan
5
Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(4), 305; https://doi.org/10.3390/pharmaceutics12040305
Received: 31 January 2020 / Revised: 23 March 2020 / Accepted: 25 March 2020 / Published: 28 March 2020
(This article belongs to the Special Issue Cell-Based Drug-Delivery Platforms)
With recent advances in cancer vaccination therapy targeting tumor-associated antigens (TAAs), dendritic cells (DCs) are considered to play a central role as a cell-based drug delivery system in the bioactive immune environment. Ex vivo generation of monocyte-derived DCs has been conventionally applied in adherent manufacturing systems with separate loading of TAAs before clinical use. We developed DCs pre-pulsed with Wilms’ tumor (WT1) peptides in low-adhesion culture maturation (WT1-DCs). Quality tests (viability, phenotype, and functions) of WT1-DCs were performed for process validation, and findings were compared with those for conventional DCs (cDCs). In comparative analyses, WT1-DCs showed an increase in viability and recovery of the DC/monocyte ratio, displaying lower levels of IL-10 (an immune suppressive cytokine) and a similar antigen-presenting ability in an in vitro cytotoxic T lymphocytes (CTLs) assay with cytomegalovirus, despite lower levels of CD80 and PD-L2. A clinical study revealed that WT1-specific CTLs (WT1-CTLs) were detected upon using the WT1-DCs vaccine in patients with cancer. A DC vaccine containing TAAs produced under an optimized manufacturing protocol is a potentially promising cell-based drug delivery system to induce acquired immunity. View Full-Text
Keywords: cell-based drug delivery; dendritic cells; tumor-associated antigens; Wilms’ tumor 1 cell-based drug delivery; dendritic cells; tumor-associated antigens; Wilms’ tumor 1
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MDPI and ACS Style

Koya, T.; Date, I.; Kawaguchi, H.; Watanabe, A.; Sakamoto, T.; Togi, M.; Kato, T., Jr.; Yoshida, K.; Kojima, S.; Yanagisawa, R.; Koido, S.; Sugiyama, H.; Shimodaira, S. Dendritic Cells Pre-Pulsed with Wilms’ Tumor 1 in Optimized Culture for Cancer Vaccination. Pharmaceutics 2020, 12, 305.

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