Systemic enhancement of antitumour immunity by peritumourally implanted immunomodulatory macroporous scaffolds.

Autor: Majedi FS; Department of Bioengineering, University of California, Los Angeles, CA, USA. majedi.negin@gmail.com.; Symphony Biosciences Inc, Los Angeles, CA, USA. majedi.negin@gmail.com., Hasani-Sadrabadi MM; Department of Bioengineering, University of California, Los Angeles, CA, USA., Thauland TJ; Department of Pediatrics, Division of Immunology, Allergy, and Rheumatology, University of California, Los Angeles, CA, USA., Keswani SG; Department of Pediatric Surgery, Texas Children's Hospital, Houston, TX, USA., Li S; Department of Bioengineering, University of California, Los Angeles, CA, USA. songli@ucla.edu., Bouchard LS; Department of Bioengineering, University of California, Los Angeles, CA, USA.; Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA., Butte MJ; Department of Pediatrics, Division of Immunology, Allergy, and Rheumatology, University of California, Los Angeles, CA, USA. mbutte@mednet.ucla.edu.; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, USA. mbutte@mednet.ucla.edu.
Jazyk: angličtina
Zdroj: Nature biomedical engineering [Nat Biomed Eng] 2023 Jan; Vol. 7 (1), pp. 56-71. Date of Electronic Publication: 2022 Dec 22.
DOI: 10.1038/s41551-022-00977-0
Abstrakt: A tumour microenvironment abundant in regulatory T (T reg ) cells aids solid tumours to evade clearance by effector T cells. Systemic strategies to suppress T reg cells or to augment immunity can elicit autoimmune side effects, cytokine storms and other toxicities. Here we report the design, fabrication and therapeutic performance of a biodegradable macroporous scaffold, implanted peritumourally, that releases a small-molecule inhibitor of transforming growth factor β to suppress T reg cells, chemokines to attract effector T cells and antibodies to stimulate them. In two mouse models of aggressive tumours, the implant boosted the recruitment and activation of effector T cells into the tumour and depleted it of T reg cells, which resulted in an 'immunological abscopal effect' on distant metastases and in the establishment of long-term memory that impeded tumour recurrence. We also show that the scaffold can be used to deliver tumour-antigen-specific T cells into the tumour. Peritumourally implanted immunomodulatory scaffolds may represent a general strategy to enhance T-cell immunity and avoid the toxicities of systemic therapies.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
Externí odkaz: