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A Proximity-Dependent Biosensor System for Visualizing Cell-Cell Interactions Induced by Therapeutic Antibodies
Yu Tang1, XiaoZhi Liao1, Yanguang Cao2
1Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC. 27599, United States.
Journal of Pharmaceutical Sciences
|December 16, 2023
Summary
Researchers developed a novel biosensor to track immune cell and cancer cell interactions during antibody therapy. This tool quantifies therapeutic antibody effects by measuring direct cell-cell contact in real-time.
Area of Science:
- Immunology
- Biotechnology
- Cancer Research
Background:
- Therapeutic antibodies show promise in cancer treatment by engaging the immune system.
- Understanding immune cell-cancer cell interactions is crucial for optimizing antibody therapy.
- Current methods have limitations in evaluating these complex interactions in real-time.
Purpose of the Study:
- To develop a novel biosensor system for evaluating direct cell-cell physical contact and interactions.
- To enable real-time monitoring and quantitative assessment of therapeutic antibody effects.
- To provide a tool for deeper characterization of antibody pharmacology.
Main Methods:
- Engineered effector and target cells with complementary luciferase subunits (SmBit and LgBit).
- Upon cell-cell contact, subunits form NanoLuc, generating a luminescent signal.
- Optimized spacer lengths for selectivity and applied the system in a 3D cell culture model.
Main Results:
- Successfully developed a biosensor system for monitoring cell-cell interactions.
- Quantitatively assessed interactions between NK and target cells with rituximab.
- Quantitatively assessed interactions between T cells and target cells with blinatumomab.
Conclusions:
- The biosensor system enables real-time, quantitative assessment of antibody-mediated cell-cell interactions.
- This technology offers potential for characterizing antibody pharmacology and optimizing cancer immunotherapy.
- Further application in physiologically relevant environments can advance our understanding of therapeutic antibodies.
