Dendritic Cell-Cytokine-Induced Killer Cells Co-Loaded with WT1/MUC1/Poly(I:C) Enhance Antitumor Immune Responses In Vitro and In Vivo

Dendritic cell-cytokine-induced killer (DC-CIK) therapy faces limitations due to antigenic heterogeneity and suboptimal immune activation. In this study, we developed a multi-antigen-loaded DC-CIK (Ag-DC-CIK) system that co-targets Wilms' tumor 1 (WT1), mucin-1 (MUC1), and the TLR3 agonist poly(I:C) to improve therapeutic outcomes. Utilizing umbilical cord blood-derived DC and CIK cells, we demonstrated that Ag-DC-CIK significantly enhanced cytotoxicity, as evidenced by the lactate dehydrogenase (LDH) assay, and increased apoptosis induction, indicated by elevated Bax and reduced Bcl-2 expression, in various tumor cell lines (HeLa, HCT116, MKN45) and organoids generated from a gastric cancer patient. Furthermore, Ag-DC-CIK effectively suppressed tumor cell migration and reduced the viability of the organoid. In MKN45 xenograft models, Ag-DC-CIK treatment inhibited tumor growth without inducing systemic toxicity, as shown by decreased Ki67 cell proliferation. This tripartite strategy synergistically enhances DC-CIK therapy by expanding antigen recognition and augmenting immune responses, presenting a promising translational approach for the treatment of gastric cancer.