Subcutaneous biodegradable scaffolds for restimulating the antitumour activity of pre-administered CAR-T cells

David K.Y. Zhang, Joshua M. Brockman, Kwasi Adu-Berchie, Yutong Liu, Yoav Binenbaum, Irene de Lázaro, Miguel C. Sobral, Rea Tresa, David J. Mooney

Research output: Contribution to journalArticlepeer-review

Abstract

The efficacy of adoptive T-cell therapies based on chimaeric antigen receptors (CARs) is limited by the poor proliferation and persistence of the engineered T cells. Here we show that a subcutaneously injected biodegradable scaffold that facilitates the infiltration and egress of specific T-cell subpopulations, which forms a microenvironment mimicking features of physiological T-cell activation, enhances the antitumour activity of pre-administered CAR-T cells. CAR-T-cell expansion, differentiation and cytotoxicity were driven by the scaffold’s incorporation of co-stimulatory bound ligands and soluble molecules, and depended on the types of co-stimulatory molecules and the context in which they were presented. In mice with aggressive lymphoma, a single, local injection of the scaffold following non-curative CAR-T-cell dosing led to more persistent memory-like T cells and extended animal survival. Injectable biomaterials with optimized ligand presentation may boost the therapeutic performance of CAR-T-cell therapies.

Original languageEnglish (US)
JournalNature Biomedical Engineering
DOIs
StateAccepted/In press - 2024

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Computer Science Applications

Fingerprint

Dive into the research topics of 'Subcutaneous biodegradable scaffolds for restimulating the antitumour activity of pre-administered CAR-T cells'. Together they form a unique fingerprint.

Cite this