Inhibition of post-surgery tumour recurrence via a hydrogel releasing CAR-T cells and anti-PDL1-conjugated platelets.
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| Abstract |
The immunosuppressive microenvironment of solid tumours reduces the antitumour activity of chimeric antigen receptor T cells (CAR-T cells). Here, we show that the release-through the implantation of a hyaluronic acid hydrogel-of CAR-T cells targeting the human chondroitin sulfate proteoglycan 4, polymer nanoparticles encapsulating the cytokine interleukin-15 and platelets conjugated with the checkpoint inhibitor programmed death-ligand 1 into the tumour cavity of mice with a resected subcutaneous melanoma tumour inhibits the local recurrence of the tumour as well as the growth of distant tumours, through the abscopal effect. The hydrogel, which functions as a reservoir, facilitates the enhanced distribution of the CAR-T cells within the surgical bed, and the inflammatory microenvironment triggers platelet activation and the subsequent release of platelet-derived microparticles. The post-surgery local delivery of combination immunotherapy through a biocompatible hydrogel reservoir could represent a translational route for preventing the recurrence of cancers with resectable tumours.
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| Authors | Quanyin Hu, Hongjun Li, Edikan Archibong, Qian Chen, Huitong Ruan, Sarah Ahn, Elena Dukhovlinova, Yang Kang, Di Wen, Gianpietro Dotti, Zhen Gu |
| Journal | Nature biomedical engineering (Nat Biomed Eng) Vol. 5 Issue 9 Pg. 1038-1047 (09 2021) ISSN: 2157-846X [Electronic] England |
| PMID | 33903744 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
| Copyright | © 2021. The Author(s), under exclusive licence to Springer Nature Limited. |
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