A genetically encoded endogenous antibody recruitment strategy for innate immune-mediated killing of cancer cells
- Author
- Justine Aelvoet (UGent) , Zifu Zhong (UGent) , Claudia Mariela Brenis Gómez (UGent) , Helena Catharine Aegerter (UGent) , Benoit Louage (UGent) , Bart Lambrecht (UGent) , Bruno De Geest (UGent) and Martijn Schuijs (UGent)
- Organization
- Project
-
- A pre-targeted nanomedicine strategy for in vivo CD8+ T cell engineering.
- A novel model of airway obstruction to spatially investigate mucus plugging in asthma and Type-2 diseases
- Role of damage associated molecular patterns (DAMPs) in initiation and persistence of chronic airway inflammation
- Understanding the immunological basis of persistent airway obstruction in asthma
- An integrated approach to unravel eosinophil function in chronic eosinophilic disorders
- JAMs - Janus Antibody-recruiting Macromolecules
- The role of alternatively-activated macrophages in the development of a lung pre-metastatic niche
- Chitinase-like proteins shaping the pulmonary metastatic niche
- Abstract
- Antibody-recruiting molecules (ARMs) are bivalent molecules that contain a cell-binding domain and an antibody-binding domain. ARMs are designed to redirect circulating endogenous antibodies from the bloodstream to the surface of cancer cells and thereby trigger innate immune-mediated killing of the latter. The current generation of clinically explored ARMs relies on synthetic small molecule haptens. However, their effectiveness is restricted by the low affinity of the available repertoire of endogenous anti-hapten antibodies. Utilizing endogenous high-affinity allergen-specific antibodies could potentially circumvent this issue. In this study, a genetically encoded antibody-recruiting strategy that utilizes lipid nanoparticles (LNPs) to deliver mRNA encoding the house dust mite allergen Der p 2, fused to a cell membrane anchor, to induce cell surface display and enable the recruitment of anti-Der p 2 antibodies, is presented. Der p 2 mRNA LNP-treated cancer cells cause greatly reduced pulmonary tumor burden in Der p 2 immunized mice, compared to untreated cells or nonimmunized mice. Reduced tumor growth is dependent on circulating antibodies, and neutrophils are identified as a key immune cell subset recognizing and eliminating Der p 2-displaying cancer cells. These findings emphasize the effectiveness of mRNA LNPs as a powerful tool for generating a genetically encoded ARM strategy, with potential applications in cancer immunotherapy.
- Keywords
- antibody, antibody-dependent cellular cytotoxicity, antibody recruiting molecules, innate immune killing, lipid nanoparticles, mRNA, tumor immunology, MESSENGER-RNA, IGG SUBCLASS, EXPRESSION, MOLECULES
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01JQEEFMQERJ7JG5AVP56KCAK7
- MLA
- Aelvoet, Justine, et al. “A Genetically Encoded Endogenous Antibody Recruitment Strategy for Innate Immune-Mediated Killing of Cancer Cells.” ADVANCED MATERIALS, vol. 37, no. 11, 2025, doi:10.1002/adma.202415468.
- APA
- Aelvoet, J., Zhong, Z., Brenis Gómez, C. M., Aegerter, H. C., Louage, B., Lambrecht, B., … Schuijs, M. (2025). A genetically encoded endogenous antibody recruitment strategy for innate immune-mediated killing of cancer cells. ADVANCED MATERIALS, 37(11). https://doi.org/10.1002/adma.202415468
- Chicago author-date
- Aelvoet, Justine, Zifu Zhong, Claudia Mariela Brenis Gómez, Helena Catharine Aegerter, Benoit Louage, Bart Lambrecht, Bruno De Geest, and Martijn Schuijs. 2025. “A Genetically Encoded Endogenous Antibody Recruitment Strategy for Innate Immune-Mediated Killing of Cancer Cells.” ADVANCED MATERIALS 37 (11). https://doi.org/10.1002/adma.202415468.
- Chicago author-date (all authors)
- Aelvoet, Justine, Zifu Zhong, Claudia Mariela Brenis Gómez, Helena Catharine Aegerter, Benoit Louage, Bart Lambrecht, Bruno De Geest, and Martijn Schuijs. 2025. “A Genetically Encoded Endogenous Antibody Recruitment Strategy for Innate Immune-Mediated Killing of Cancer Cells.” ADVANCED MATERIALS 37 (11). doi:10.1002/adma.202415468.
- Vancouver
- 1.Aelvoet J, Zhong Z, Brenis Gómez CM, Aegerter HC, Louage B, Lambrecht B, et al. A genetically encoded endogenous antibody recruitment strategy for innate immune-mediated killing of cancer cells. ADVANCED MATERIALS. 2025;37(11).
- IEEE
- [1]J. Aelvoet et al., “A genetically encoded endogenous antibody recruitment strategy for innate immune-mediated killing of cancer cells,” ADVANCED MATERIALS, vol. 37, no. 11, 2025.
@article{01JQEEFMQERJ7JG5AVP56KCAK7,
abstract = {{Antibody-recruiting molecules (ARMs) are bivalent molecules that contain a cell-binding domain and an antibody-binding domain. ARMs are designed to redirect circulating endogenous antibodies from the bloodstream to the surface of cancer cells and thereby trigger innate immune-mediated killing of the latter. The current generation of clinically explored ARMs relies on synthetic small molecule haptens. However, their effectiveness is restricted by the low affinity of the available repertoire of endogenous anti-hapten antibodies. Utilizing endogenous high-affinity allergen-specific antibodies could potentially circumvent this issue. In this study, a genetically encoded antibody-recruiting strategy that utilizes lipid nanoparticles (LNPs) to deliver mRNA encoding the house dust mite allergen Der p 2, fused to a cell membrane anchor, to induce cell surface display and enable the recruitment of anti-Der p 2 antibodies, is presented. Der p 2 mRNA LNP-treated cancer cells cause greatly reduced pulmonary tumor burden in Der p 2 immunized mice, compared to untreated cells or nonimmunized mice. Reduced tumor growth is dependent on circulating antibodies, and neutrophils are identified as a key immune cell subset recognizing and eliminating Der p 2-displaying cancer cells. These findings emphasize the effectiveness of mRNA LNPs as a powerful tool for generating a genetically encoded ARM strategy, with potential applications in cancer immunotherapy.}},
author = {{Aelvoet, Justine and Zhong, Zifu and Brenis Gómez, Claudia Mariela and Aegerter, Helena Catharine and Louage, Benoit and Lambrecht, Bart and De Geest, Bruno and Schuijs, Martijn}},
issn = {{0935-9648}},
journal = {{ADVANCED MATERIALS}},
keywords = {{antibody,antibody-dependent cellular cytotoxicity,antibody recruiting molecules,innate immune killing,lipid nanoparticles,mRNA,tumor immunology,MESSENGER-RNA,IGG SUBCLASS,EXPRESSION,MOLECULES}},
language = {{eng}},
number = {{11}},
title = {{A genetically encoded endogenous antibody recruitment strategy for innate immune-mediated killing of cancer cells}},
url = {{http://doi.org/10.1002/adma.202415468}},
volume = {{37}},
year = {{2025}},
}
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