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Updated: May 23, 2026
08:04
In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function
Published on: February 27, 2019
Marker-Agnostic Tumor Anchoring Chimeras Enable pH-Gated Immune Engagement
Heleen Lauwers1, Jamie De Baere1, Ilke Aernout2
1Department of Pharmaceutics, Ghent University, Belgium, Cancer Research Institute Ghent (CRIG), Ghent, Belgium.
Angewandte Chemie (International Ed. in English)
|May 22, 2026
Summary
Researchers developed pH-sensitive fusion proteins called MATRACs (Marker-Agnostic Tumor Anchoring Chimeras) to target cancer cells by exploiting tumor acidosis, enabling antigen-independent immune engagement for new immunotherapies.
Area of Science:
- Oncology
- Immunology
- Biochemistry
Background:
- Current cancer immunotherapies rely on cell surface antigens, but many tumors lack specific markers or downregulate them.
- Tumor acidosis, an acidic extracellular tumor microenvironment (TME), is a common feature of solid cancers due to metabolic dysregulation.
Purpose of the Study:
- To develop a novel, antigen-independent strategy for cancer immunotherapy by targeting tumor acidosis.
- To create pH-sensitive fusion proteins, termed MATRACs, for immune cell engagement.
Main Methods:
- Utilized the diphtheria toxin translocation domain (tdDT) and its pH-dependent conformational switch for membrane anchoring.
- Engineered a fluorescein-tagged tdDT-Fc variant to anchor to acidic tumor cells and recruit engineered immune cells (CAR T cells).
Main Results:
- Demonstrated that tdDT-based proteins selectively anchor to cells in acidic conditions mimicking the TME.
- Showcased pH-dependent immune activation by recruiting antifluorescein CAR T cells to tumor cells via the fluorescein-tagged MATRAC.
Conclusions:
- Established tdDT-based MATRACs as a modular platform for antigen-agnostic immune engagement.
- MATRACs offer a TME-responsive approach for next-generation, pH-targeted cancer immunotherapies.
