Mucin 1 Antigen Mimetic Functionalized Mannosylated Peptide Nanofibers for Antigen Uptake and Immune Modulation

Abstract

In this work, immune modulation of the monocyte-derived dendritic cells was studied by 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) displayed remarkable cell-penetrating capabilities, allowed the correct presentation of the antigen mimetic with a corresponding induction of lymphocytes, iNKT and NK cells recruitment. The Man-PA/Tn-MIM integrated nanofibrers were also found to direct immune response towards Th1 phenotype which is responsible for the production of cellular and humoral immunity. Organ-on-chip tests confirmed the cytotoxicity of lymphocytes stimulated with DC exposed to Man-PA/Tn-MIM. These results will help in the development of immunotherapies avoiding complications due to heterogeneous antigen display and to the use of adjuvants.