title: Enhancing immunostimulatory function of human embryonic stem cell-derived dendritic cells by CD1d overexpression.
abstract: Human embryonic stem cell-derived dendritic cells (hESC-DCs) may potentially provide a platform to generate "off-the-shelf" therapeutic cancer vaccines. To apply hESC-DCs for cancer immunotherapy in a semiallogeneic setting, it is crucial for these cells to "jump-start" adaptive antitumor immunity before their elimination by host alloreaction. In this study, we investigated whether CD1d upregulation in hESC-DCs may exploit invariant NKT (iNKT) cell adjuvant activity and boost antitumor immunity. Using a baculoviral vector carrying the CD1d gene, we produced CD1d-overexpressing hESC-DCs and demonstrated that the upregulated CD1d was functional in presenting α-galactosylceramide for iNKT cell expansion. Pulsed with melanoma Ag recognized by T cell 1 peptide, the CD1d-overexpressing hESC-DCs displayed enhanced capability to prime CD8(+) T cells without relying on α-galactosylceramide loading. Blocking the CD1d with Ab reduced the immunogenicity, suggesting the importance of hESC-DC and iNKT cell interaction in this context. The CD1d-overexpressing hESC-DCs also induced a proinflammatory cytokine profile that may favor the T cell priming. Moreover, a similar immunostimulatory effect was observed when the CD1d upregulation strategy was applied in human monocyte-derived dendritic cells. Therefore, our study suggests that the upregulation of CD1d in hESC-DCs provides a novel strategy to enhance their immunogenicity. This approach holds potential for advancing the application of hESC-DCs into human cancer immunotherapy.
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore, Singapore 138669. jmzeng@ibn.a-star.edu.sg
authors.forename: Jieming
authors.initials: J
authors.lastname: Zeng
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shahbazi
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Wu
authors.forename: Han Chong
authors.initials: HC
authors.lastname: Toh
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
chemical_list: D055610:Antigens, CD1d; D000951:Antigens, Neoplasm; C526877:CD1D protein, human; D019496:Cancer Vaccines