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Generation of a Human iPSC-Based Blood-Brain Barrier Chip

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Published on: March 2, 2020

Organ-on-chip for advancing CAR therapy.

Lightson Ngashangva¹, Sunil Martin²

¹Biosensors and Biomicrofluidics Laboratory, Transdisciplinary Biology Program Rajiv Gandhi Centre for Biotechnology (RGCB) Thiruvananthapuram Kerala India.

Clinical & Translational Immunology

|February 28, 2025

Summary

CAR therapy shows high relapse rates and toxicity in blood cancers. Organ-on-chip models offer a promising alternative to animal testing for evaluating cell and gene therapies in human-relevant systems.

Keywords:

CAR therapy microfluidics organ‐on‐chip tumor immune microenvironment

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Area of Science:

Biomedical Engineering
Immunotherapy
Toxicology

Background:

Chimeric Antigen Receptor (CAR) therapy faces challenges with high relapse rates (over 60%) and significant off-tumor toxicities in blood malignancies.
Current models struggle to replicate the complex tumor microenvironment (TME) and accurately predict CAR therapy's adverse effects.
Regulatory shifts encourage replacing animal testing with human-relevant cell culture systems.

Purpose of the Study:

To explore the potential of organ-on-chip (OOC) technology for evaluating CAR therapy.
To address the limitations of existing models in predicting CAR therapy's efficacy and toxicity.
To investigate microfluidics-based systems for real-time cell and gene therapy testing.

Main Methods:

Utilizing microfluidics technology to create organ-on-chip (OOC) models.
Emulating physiological conditions, including blood and lymph flow dynamics at the microscale.
Developing platforms for assessing cell and gene therapies in a human-relevant context.

Main Results:

OOC technology holds potential for mimicking complex biological systems relevant to CAR therapy.
Microfluidic platforms can potentially capture intricate biochemical and biophysical aspects of the TME.
The application of OOC for real-time cell and gene therapy evaluation is an emerging area.

Conclusions:

Organ-on-chip systems represent a significant advancement for preclinical evaluation of cell and gene therapies like CAR therapy.
This technology offers a path towards more accurate prediction of therapeutic outcomes and toxicities.
Further development is needed to fully realize the potential of microfluidics in real-time cell and gene therapy testing.