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Updated: Oct 2, 2025
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Published on: November 30, 2016
Metabolic labelling of cancer cells with glycodendrimers stimulate immune-mediated cytotoxicity
David Goyard1, Peremobowei Iyanu Diriwari1, Nathalie Berthet1
1Univ. Grenoble Alpes, CNRS DCM UMR 5250 F-38000 Grenoble France nathalie.berthet@univ-grenoble-alpes.fr.
Abstract:
The recruitment of antibody naturally present in human blood stream at the surface of cancer cells have been proved a promising immunotherapeutic strategy to fight cancer. Antibody recruiting molecules (ARMs) combining tumor and antibody binding modules have been developed for this purpose, however the formation of the interacting complex with both antibody and cell is difficult to optimize to stimulate immune-mediated cytotoxicity. To circumvent this limitation, we report herein a more direct approach combining cell metabolism of azido-sugar and bio-orthogonal click chemistry to conjugate at the cell glycocalyx structurally well-defined glycodendrimers as antibody binding module (ABM). We demonstrate that this strategy allows not only the recruitment of natural antibody at the surface of isolated cells or solid tumor models but also activate a cytotoxic response with human serum as unique source of immune effectors.
Insights
This study introduces a novel cancer immunotherapy approach using bio-orthogonal click chemistry to recruit natural antibodies to cancer cells, activating immune responses without complex molecular engineering.
Area of Science:
- Immunotherapy
- Bioconjugation Chemistry
- Cancer Biology
Background:
- Recruiting natural antibodies to cancer cells is a promising immunotherapy strategy.
- Existing antibody recruiting molecules (ARMs) face challenges in optimizing complex formation for effective immune response.
Purpose of the Study:
- To develop a direct method for recruiting natural antibodies to cancer cells using bio-orthogonal click chemistry.
- To enable antibody binding module (ABM) conjugation to the cell glycocalyx via cell metabolism of azido-sugar.
Main Methods:
- Utilized cell metabolism of azido-sugar for glycan modification.
- Employed bio-orthogonal click chemistry for precise ABM conjugation to the cell surface.
- Tested the strategy on isolated cells and solid tumor models.
Main Results:
- Successfully recruited natural antibodies to the surface of cancer cells.
- Demonstrated activation of a cytotoxic immune response using only human serum.
- Validated the approach in both isolated cell and solid tumor models.
Conclusions:
- This direct conjugation strategy effectively recruits natural antibodies to cancer cells.
- The method activates immune-mediated cytotoxicity, offering a simplified immunotherapeutic approach.
- The technique shows potential for fighting cancer by leveraging the body's natural immune defenses.
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