Assessment of CAR-T cell-mediated cytotoxicity in 3D microfluidic cancer co-culture models for combination therapy

Karla Paterson, Sarah Paterson, Theresa Mulholland, Seth B. Coffelt, Michele Zagnoni

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)
20 Downloads (Pure)

Abstract

Chimeric antigen receptor (CAR)-T cell therapy is efficacious against many haematological malignancies, but challenges remain when using this cellular immunotherapy for treating solid tumours. Classical 2D in vitro models fail to recapitulate the complexity of the tumour microenvironment, whilst in vivo models, such as patient-derived xenografts, are costly and labour intensive. Microfluidic technologies can provide miniaturized solutions to assess CAR-T therapies in 3D complex preclinical models of solid tumours. Here, we present a novel microfluidic immunoassay for the evaluation of CAR-T cell cytotoxicity and targeting specificity on 3D spheroids containing cancer cells and stromal cells. Monitoring the interaction between CAR-T cells and spheroid co-cultures, we show that CAR-T cells home towards target-expressing cancer cells and elicit a cytotoxic effect. Testing CAR-T cells in combination therapies, we show that CAR-T cell cytotoxicity is enhanced with anti-PD-L1 therapy and carboplatin chemotherapy. We propose this proof-of-concept microfluidic immunoassay as a material-saving, pre-clinical screening tool for quantification of cell therapy efficacy.
Original languageEnglish
Pages (from-to)86-95
Number of pages10
JournalIEEE Open Journal of Engineering in Medicine and Biology
Volume3
DOIs
Publication statusPublished - 27 May 2022

Keywords

  • immunotherapy
  • Lab-on-a-chip
  • solid tumour microenvironments
  • 3D in vitro complex model

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