A multilayered blood vessel/tumor tissue chip to investigate T cell infiltration into solid tumor tissues

Lee, Jaehyun; Kim, Seong‐Eun; Moon, Dowon; Doh, Junsang

doi:10.1039/d1lc00182e

Cited by 41 publications

(30 citation statements)

References 63 publications

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“…Hydrogels can be classified into naturally derived, synthetic, and hybrid. Natural hydrogels include collagen [ 28 , 111 , 248 ], Matrigel TM [ 242 , 249 ], fibrin [ 250 , 251 ], and alginate, [ 101 , 252 , 253 ]. Alternatively, synthetic hydrogel counterparts are commonly comprised of polyacrylamide (PAAm) [ 254 ] and polyethylene glycol (PEG) [ 255 ].…”

Section: Preclinical Models For Trafficking and Infiltrationmentioning

confidence: 99%

“…Not only can the organoids recapitulate original tissue histologically and genetically, but they also have the ability to self-organize, differentiate, and function in response to mechanical and chemical cues [ 276 , 277 ]. Organoids are widely cultured in 3D in various platforms such as static ECM-embedment culture [ 237 ], microfluidic devices [ 248 ], and 3D bioprinting [ 275 ]. In one study, co-culture of CAR-engineered natural killer cells (EPCAM-CAR NK-92) and patient-derived colon organoids on the Matrigel matrix demonstrated an increase in immune cell migration and cytotoxicity against cancer cells [ 239 ].…”

Section: Preclinical Models For Trafficking and Infiltrationmentioning

confidence: 99%

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CAR T Cell Locomotion in Solid Tumor Microenvironment

Nguyen

Ogando‐Rivas

Liu

et al. 2022

Cells

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The promising outcomes of chimeric antigen receptor (CAR) T cell therapy in hematologic malignancies potentiates its capability in the fight against many cancers. Nevertheless, this immunotherapy modality needs significant improvements for the treatment of solid tumors. Researchers have incrementally identified limitations and constantly pursued better CAR designs. However, even if CAR T cells are armed with optimal killer functions, they must overcome and survive suppressive barriers imposed by the tumor microenvironment (TME). In this review, we will discuss in detail the important role of TME in CAR T cell trafficking and how the intrinsic barriers contribute to an immunosuppressive phenotype and cancer progression. It is of critical importance that preclinical models can closely recapitulate the in vivo TME to better predict CAR T activity. Animal models have contributed immensely to our understanding of human diseases, but the intensive care for the animals and unreliable representation of human biology suggest in vivo models cannot be the sole approach to CAR T cell therapy. On the other hand, in vitro models for CAR T cytotoxic assessment offer valuable insights to mechanistic studies at the single cell level, but they often lack in vivo complexities, inter-individual heterogeneity, or physiologically relevant spatial dimension. Understanding the advantages and limitations of preclinical models and their applications would enable more reliable prediction of better clinical outcomes.

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Section: Preclinical Models For Trafficking and Infiltrationmentioning

confidence: 99%

Section: Preclinical Models For Trafficking and Infiltrationmentioning

confidence: 99%

CAR T Cell Locomotion in Solid Tumor Microenvironment

Nguyen

Ogando‐Rivas

Liu

et al. 2022

Cells

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“…With respect to off-chip CAR-T screening approaches, microfluidic technology can be effective in increasing the complexity of the 3D tumour models and the data throughput of the assays when performing combination therapy studies whilst using small sample volumes. Miniaturized 3D immunoassays have been developed using microfluidic and lab-on-a-chip technology, [20][21][22][23][24][25][26][27][28][29] yet their application is still limited in relation to CAR-T studies. [30] For example, Ando et al established a microfluidic assay to study the effect of hypoxic conditions on CAR-T cell behaviour.…”

Section: Himericmentioning

confidence: 99%

Assessment of CAR-T Cell-Mediated Cytotoxicity in 3D Microfluidic Cancer Co-Culture Models for Combination Therapy

Paterson

Paterson²,

Mulholland³

et al. 2022

IEEE Open J. Eng. Med. Biol.

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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 materialsaving, pre-clinical screening tool for quantification of cell therapy efficacy. Index Terms -Immunotherapy, Lab-on-a-chip, Solid Tumour Microenvironment, Three-dimensional in vitro complex model. Impact Statement-Microfluidic platforms and protocols canprovide powerful, cost-effective and miniaturised in vitro assays to preclinically assess CAR-T cell therapies in solid tumours.

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“…B. W. bin Lee et al, 2019 ), heart ( Liu et al, 2020 ; Ren et al, 2020 ; F. Zhang et al, 2021 ), kidney ( Lin et al, 2020 , Lin et al, 2020 ; Theobald et al, 2018 ), blood vessels ( Cao et al, 2019 ; Lee et al, 2021 ) and even the whole body ( Chen et al, 2018 ) can be mimicked on microfluidic devices, which results in more predictable outcomes for drug screening. These outstanding characteristics make microfluidic systems an ideal choice for highly sensitive drug sensing and screening.…”

Section: Introductionmentioning

confidence: 99%