Pharmaceutics (Mar 2020)

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

  • Terutsugu Koya,
  • Ippei Date,
  • Haruhiko Kawaguchi,
  • Asuka Watanabe,
  • Takuya Sakamoto,
  • Misa Togi,
  • Tomohisa Kato,
  • Kenichi Yoshida,
  • Shunsuke Kojima,
  • Ryu Yanagisawa,
  • Shigeo Koido,
  • Haruo Sugiyama,
  • Shigetaka Shimodaira

DOI
https://doi.org/10.3390/pharmaceutics12040305
Journal volume & issue
Vol. 12, no. 4
p. 305

Abstract

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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.

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