Open AccessInhibition of post-surgery tumour recurrence via a hydrogel releasing CAR-T cells and anti-PDL1-conjugated platelets
Author(s) -
Quanyin Hu,
Hongjun Liu,
Edikan Archibong,
Qian Chen,
Huitong Ruan,
Sarah Ahn,
Elena Dukhovlinova,
Yang Kang,
Di Wen,
Gianpietro Dotti,
Zhen Gu
Publication year - 2021
Publication title -
nature biomedical engineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.961
H-Index - 56
ISSN - 2157-846X
DOI - 10.1038/s41551-021-00712-1
Subject(s) - tumor microenvironment , immunotherapy , platelet , cancer research , melanoma , hyaluronic acid , chemistry , abscopal effect , platelet activation , cytokine , chimeric antigen receptor , immune system , medicine , immunology , anatomy
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.