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

• Published in: Science advances 2024-12, Vol.10 (50), p.eadm7928
• Main Authors: Li, Shuyi, Yao, Zhi-Cheng, Wang, Hanzhi, Ecker, Jonathan A, Omotoso, Mary O, Lee, Jaechan, Kong, Jiayuan, Feng, Hexiang, Chaisawangwong, Worarat, Kang, Si-Sim, Shannon, Sydney R, Livingston, Natalie K, Bieler, Joan G, Singh, Shweta, Zhang, Maya L, O'Neal, Pilar, Ariail, Emily, Biggs, Benjamin, Hickey, John W, Mao, Hai-Quan, Schneck, Jonathan P
• Format: Article
• Language: English
• Subjects: Animals; Antigen-Presenting Cells - immunology; CD8-Positive T-Lymphocytes - immunology; Humans; Hyaluronic Acid - chemistry; Hydrogels - chemistry; Immunologic Memory; Immunotherapy - methods; Memory T Cells - immunology; Mice; Nanoparticles - chemistry; Neoplasms - immunology; Neoplasms - therapy
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.adm7928

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