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Adoptive T cell transfer and host antigen-presenting cell recruitment with cryogel scaffolds promotes long-term protection against solid tumors.

Authors :
Adu-Berchie, Kwasi
Brockman, Joshua M.
Liu, Yutong
To, Tania W.
Zhang, David K. Y.
Najibi, Alexander J.
Binenbaum, Yoav
Stafford, Alexander
Dimitrakakis, Nikolaos
Sobral, Miguel C.
Dellacherie, Maxence O.
Mooney, David J.
Source :
Nature Communications; 6/15/2023, Vol. 14 Issue 1, p1-15, 15p
Publication Year :
2023

Abstract

Although adoptive T cell therapy provides the T cell pool needed for immediate tumor debulking, the infused T cells generally have a narrow repertoire for antigen recognition and limited ability for long-term protection. Here, we present a hydrogel that locally delivers adoptively transferred T cells to the tumor site while recruiting and activating host antigen-presenting cells with GMCSF or FLT3L and CpG, respectively. T cells alone loaded into these localized cell depots provided significantly better control of subcutaneous B16-F10 tumors than T cells delivered through direct peritumoral injection or intravenous infusion. T cell delivery combined with biomaterial-driven accumulation and activation of host immune cells prolonged the activation of the delivered T cells, minimized host T cell exhaustion, and enabled long-term tumor control. These findings highlight how this integrated approach provide both immediate tumor debulking and long-term protection against solid tumors, including against tumor antigen escape. Adoptive T cell therapy has shown remarkable promise for the treatment of haematological malignancies. Here, the authors show that a cryogel platform for the simultaneous delivery of autologous T cells and recruitment of local antigen-presenting cells promotes long-lasting responses against solid tumours in mice. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20411723
Volume :
14
Issue :
1
Database :
Complementary Index
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
164355692
Full Text :
https://doi.org/10.1038/s41467-023-39330-7