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

Shuyi Li; Zhi-Cheng Yao; Hanzhi Wang; Jonathan A Ecker; Mary O Omotoso; Jaechan Lee; Jiayuan Kong; Hexiang Feng; Worarat Chaisawangwong; Si-Sim Kang; Sydney R Shannon; Natalie K Livingston; Joan G Bieler; Shweta Singh; Maya L Zhang; Pilar O'Neal; Emily Ariail; Benjamin Biggs; John W Hickey; Hai-Quan Mao; Jonathan P Schneck

doi:10.1126/sciadv.adm7928

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

Sci Adv. 2024 Dec 13;10(50):eadm7928. doi: 10.1126/sciadv.adm7928. Epub 2024 Dec 13.

Authors

Shuyi Li^{1

2

3}, Zhi-Cheng Yao^{2

4

5}, Hanzhi Wang⁶, Jonathan A Ecker⁷, Mary O Omotoso^{1

8}, Jaechan Lee⁹, Jiayuan Kong^{2

4

5}, Hexiang Feng^{2

5

6}, Worarat Chaisawangwong¹, Si-Sim Kang¹, Sydney R Shannon^{1

5

8}, Natalie K Livingston^{1

2

5

8}, Joan G Bieler¹, Shweta Singh¹, Maya L Zhang², Pilar O'Neal⁸, Emily Ariail^{1

5

8}, Benjamin Biggs^{1

8}, John W Hickey¹⁰, Hai-Quan Mao^{2

3

4

5

8}, Jonathan P Schneck^{1

3

8

11}

Affiliations

¹ Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
² Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
³ Johns Hopkins Translational Immunoengineering Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁴ Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA.
⁵ Translational Tissue Engineering Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁶ Department of Biomedical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA.
⁷ Department of Biology, Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD, USA.
⁸ Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁹ Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA.
¹⁰ Department of Biomedical Engineering, Duke University, Durham, NC, USA.
¹¹ Institute for Cell Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Abstract

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.

MeSH terms

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

Substances

Hydrogels
Hyaluronic Acid