AI Article Synopsis

  • Combination immunotherapy is gaining traction as a way to improve immune checkpoint inhibitor effectiveness in breast cancer, addressing issues with the tumor microenvironment's complexity.
  • A new innovation, the tumor-microenvironment-on-chip (TMoC), mimics real tumor conditions, allowing for better drug screening and understanding T cell interactions with tumors.
  • The TMoC has shown promising results in testing combinations of targeted and chemotherapy drugs alongside immunotherapy, closely aligning with responses seen in animal models, highlighting its potential for improving drug development and treatment strategies.

Article Abstract

Combination immunotherapy has emerged as a promising strategy to address the challenges associated with immune checkpoint inhibitor (ICI) therapy in breast cancer. The efficacy of combination immunotherapy hinges upon the intricate and dynamic nature of the tumor microenvironment (TME), characterized by cellular heterogeneity and molecular gradients. However, current methodologies for drug screening often fail to accurately replicate these complex conditions, resulting in limited predictive capacity for treatment outcomes. Here, a tumor-microenvironment-on-chip (TMoC), integrating a circulation system and ex vivo tissue culture with physiological oxygen and nutrient gradients, is described. This platform enables spatial infiltration of cytotoxic CD8 T cells and their targeted attack on the tumor, while preserving the high complexity and heterogeneity of the TME. The TMoC is employed to assess the synergistic effect of five targeted therapy drugs and five chemotherapy drugs in combination with immunotherapy, demonstrating strong concordance between chip and animal model responses. The TMoC holds significant potential for advancing drug development and guiding clinical decision-making, as it offers valuable insights into the complex dynamics of the TME.

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Source
http://dx.doi.org/10.1002/adhm.202302268DOI Listing

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