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The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
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Visualizing cell-cell communication using synthetic notch activated MRI.

TianDuo Wang1,2, Yuanxin Chen2, Nivin N Nystrom1,2

  • 1Department of Medical Biophysics, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 3K7, Canada.

Proceedings of the National Academy of Sciences of the United States of America
|March 9, 2023
PubMed
Summary
This summary is machine-generated.

Researchers developed a new imaging system to track engineered immune cells targeting cancer. This technology uses reporter genes to visualize immune cell interactions with tumors noninvasively, aiding cell therapy development.

Keywords:
MRIcell therapycell–cell communicationreporter genesynthetic Notch

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Area of Science:

  • Immunology and Cancer Biology
  • Biomedical Imaging and Biotechnology

Background:

  • Cell-cell communication is crucial for multicellular life and cancer immunotherapy.
  • Effective cancer immunotherapies require precise targeting of cancer cells by immune cells.
  • Noninvasive imaging is needed to monitor immune cell behavior and therapy efficacy.

Purpose of the Study:

  • To develop an imaging strategy for visualizing immune-cancer cell interactions in real-time.
  • To engineer immune cells that report on their engagement with specific cancer antigens.
  • To enable spatiotemporal monitoring of cell-based therapies.

Main Methods:

  • Engineered T cells using the synthetic Notch (SynNotch) system to express reporter genes (optical and MRI) upon CD19 antigen recognition.
  • Utilized magnetic resonance imaging (MRI) and bioluminescence imaging (BLI) to detect reporter gene expression in vivo.
  • Extended the SynNotch system to human natural killer (NK-92) cells for broader applicability.

Main Results:

  • Engineered T cells showed antigen-dependent reporter gene expression in CD19-positive tumors in mice.
  • MRI clearly visualized OATP1B3-expressing T cells within tumors, mapping their distribution.
  • Engineered NK-92 cells exhibited similar antigen-dependent reporter activity and were detectable via BLI in a systemic cancer model.

Conclusions:

  • The modular SynNotch-based imaging strategy enables noninvasive visualization of engineered immune cell interactions with tumors.
  • This technology facilitates antigen-specific tracking of cell therapies, with potential for clinical translation.
  • The imaging approach can enhance understanding of cell interactions in disease and normal physiology.