Ex vivo expansion and hydrogel-mediated in vivo delivery of tissue-resident memory T cells for immunotherapy
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.
Authors
- Hexiang Feng
- Hai‐Quan Mao (ORCID: https://orcid.org/0000-0002-4262-9988)
- Natalie K. Livingston (ORCID: https://orcid.org/0000-0002-0909-9284)
- Joan Glick Bieler (ORCID: https://orcid.org/0000-0002-7667-1965)
- Judy J. Lee (ORCID: https://orcid.org/0009-0006-4533-2465)
- Zhi‐Cheng Yao (ORCID: https://orcid.org/0000-0002-3086-6038)
- Jiayuan Kong (ORCID: https://orcid.org/0000-0002-5368-8940)
- Emily Ariail
- Sydney R. Shannon (ORCID: https://orcid.org/0000-0003-0474-0869)
- John W. Hickey (ORCID: https://orcid.org/0000-0001-9961-7673)
- Jonathan P. Schneck (ORCID: https://orcid.org/0000-0001-5346-2776)
- Si-Sim Kang (ORCID: https://orcid.org/0000-0001-9448-447X)
- Worarat Chaisawangwong (ORCID: https://orcid.org/0000-0003-2400-6186)
- Mary O. Omotoso (ORCID: https://orcid.org/0000-0001-5560-167X)
- Maya L. Zhang (ORCID: https://orcid.org/0009-0007-6288-2669)
- S.-H. Li (ORCID: https://orcid.org/0000-0002-9832-9159)
- Patrick D. O’Neal
- Shweta Singh (ORCID: https://orcid.org/0000-0003-2800-1198)
- Hanzhi Wang (ORCID: https://orcid.org/0009-0001-4577-0864)
- Jennifer L. Ecker
- Benjamin Biggs (ORCID: https://orcid.org/0009-0003-6844-0280)
Institutions
- Johns Hopkins University (US)
- Duke University (US)
- Johns Hopkins Medicine (US)
Publication Details
- Journal
- Science Advances
- Published
- 2024-12-13
- DOI
- https://doi.org/10.1126/sciadv.adm7928
- Citations
- 7
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 1.98