Mucin 1 antigen mimetic functionalized mannosylated peptide nanofibers for antigen uptake and immune modulation

: In this work, immune modulation of monocyte-derived dendritic cells was studied using in vitro cell culture and organ-on-chip models. Self-assembled mannosylated peptide nanofibers were prepared and integrated with the MUC1 TnThr mimetic Tn-MIM, to stimulate DCs' maturation and differentiation. The nanofibers obtained (namely Man-PA/Tn-MIM) showed remarkable cell-penetrating capabilities and allowed the correct presentation of the antigen mimetic with a corresponding induction of lymphocyte, iNKT and NK cell recruitment. The Man-PA/Tn-MIM integrated nanofibers were also found to direct the immune response towards the Th1 phenotype, which is responsible for the production of cellular and humoral immunity. Organ-on-chip tests confirmed the cytotoxicity of lymphocytes stimulated with DCs exposed to Man-PA/Tn-MIM. These results will help in the development of immunotherapies avoiding complications due to heterogeneous antigen presentation and the use of adjuvants.