Ex vivo expansion and hydrogel-mediated in vivo delivery of tissue-resident memory T cells for immunotherapy.

Tissue-resident memory T (T_RM) cells preferentially reside in peripheral tissues, serving as key players in tumor immunity and immunotherapy. The lack of effective approaches for expanding T_RM cells and delivering these cells in vivo hinders the exploration of T_RM cell-mediated cancer immunotherapy. Here, we report a nanoparticle artificial antigen-presenting cell (nano-aAPC) ex vivo expansion approach and an in vivo delivery system for T_RM cells. Using the nano-aAPC platform, we expanded functional antigen-specific murine and human T_RM-like CD8⁺ T cells ex vivo. We also developed an injectable macroporous hyaluronic acid (HA) hydrogel to deliver T_RM-like cells. T_RM-like cells delivered in the optimized HA hydrogel trigger robust local and systemic antitumor immunity and show synergistic effects with anti-PD-1 treatment. Our findings suggest that nano-aAPC-induced T_RM-like cells, coupled with a hydrogel delivery system, offer an efficient way to advance the understanding of T_RM cell-mediated cancer therapy.

Duke Scholars

Author John Wirthlin Hickey Biomedical Engineering