FunctionalizedPoly(ethylene Glycol) Diacrylate Scaffoldsfor <i>In Situ</i> Immunomodulation of Dendritic Cells TargetingMelanoma Tumor

Various immunotherapeutic strategies are being developed to fight cancer, which is one of the leading causes of mortality. Dendritic cells (DCs), being professional antigen-presenting cells, after efficient manipulation with tumor-associated antigens, can lead to effective T-cell recruitment and activation at the tumor site, resulting in cytotoxic T-cell-mediated cancer cell killing. To circumvent the inefficiencies of <i>ex vivo</i> DC modification and patient infusion, an alternative strategy involving <i>in situ</i> DC activation has been explored here. Here, the vaccine components are tumor lysates, as antigens, and polyinosinic:polycytidylic acid (poly(I:C)), a toll-like receptor-3 (TLR3) agonist, as an adjuvant. Our <i>in vitro</i> studies demonstrate that complexing poly(I:C) with a carrier molecule, chitosan, enhances its stability and accessibility to TLR3 in the DC endosomal membrane. Material-based localized delivery of immunomodulatory factors is known to improve their stability and reduce their off-target side effects. Here, PEGDA–PLL-based macroporous scaffolds allow easy recruitment of host cells, thereby enabling effective interaction between the vaccine components loaded on them and the infiltrating immune cells. The vaccine components present in the scaffold facilitate efficient DC activation and migration, leading to subsequent T-cell activation and antitumor response, as shown by our <i>in vivo</i> studies.