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

Li, Shuyi; Yao, Zhi-Cheng; Wang, Hanzhi; Ecker, Jonathan A; Omotoso, Mary O; Lee, Jaechan; Kong, Jiayuan; Feng, Hexiang et al. · Sci Adv · 2024

basic_science · Level V

Where this comes from

Abstract

Tissue-resident memory T (T<sub>RM</sub>) cells preferentially reside in peripheral tissues, serving as key players in tumor immunity and immunotherapy. The lack of effective approaches for expanding T<sub>RM</sub> cells and delivering these cells in vivo hinders the exploration of T<sub>RM</sub> 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<sub>RM</sub> cells. Using the nano-aAPC platform, we expanded functional antigen-specific murine and human T<sub>RM</sub>-like CD8<sup>+</sup> T cells ex vivo. We also developed an injectable macroporous hyaluronic acid (HA) hydrogel to deliver T<sub>RM</sub>-like cells. T<sub>RM</sub>-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<sub>RM</sub>-like cells, coupled with a hydrogel delivery system, offer an efficient way to advance the understanding of T<sub>RM</sub> cell-mediated cancer therapy.

Medical subject headings