DNA-based artificial dendritic cells for in situ cytotoxic T cell stimulation and immunotherapy.

Abstract

In immunotherapy, ex vivo stimulation of T cells requires significant resources and effort. Here, we report artificial dendritic cell-mimicking DNA microflowers (DM) for programming T cell stimulation in situ. To mimic dendritic cells, DNA-based artificial dendritic microflowers were constructed, surface-coated with polydopamine, and further modified with anti-CD3 and anti-CD28 antibodies to yield antibody-modified DM (DM-A). The porous structure of DM-A allowed entrapment of the T cell-stimulating cytokine, ineterleukin-2, yielding interleukin-2-loaded DM-A (DM-AI). For comparison, polystyrene microparticles coated with polydopamine and modified with anti-CD3 and anti-CD28 antibodies (PS-A) were used. Compared to PS-A, DM-AI showed significantly greater contact with T cell surfaces. DM-AI provided the highest ex vivo expansion of cytotoxic T cells. Local injection of DM-AI to tumor tissues induced the recruitment of T cells and expansion of cytotoxic T cells in tumor microenvironments. Unlike the other groups, model animals injected with DM-AI did not exhibit growth of primary tumors. Treatment of mice with DM-AI also protected against growth of a rechallenged distant tumor, and thus prevented tumor recurrence in this model. DM-AI has great potential for programmed stimulation of CD8⁺ T cells. This concept could be broadly extended for the programming of specific T cell stimulation profiles.