Preclinical toxicological assessment of an α-galactosylceramide-adjuvanted mRNA cancer vaccine in Wistar Han rats and domestic pigs
- Author
- Sofie Meulewaeter, Margo De Velder (UGent) , Diethard Reckelbus (UGent) , Kevin Mwangi (UGent) , Thomas Ehouarne (UGent) , Ilke Aernout (UGent) , Yanou Engelen (UGent) , Fëllanza Halimi (UGent) , Isis Van herteryck (UGent) , Lobke De Bels (UGent) , Valerie Redant, Louise De la Mane (UGent) , Joline Ingels (UGent) , Bo Coppens (UGent) , Serge Van Calenbergh (UGent) , Pieter Cornillie (UGent) , Gabriële Holtappels (UGent) , Benedicte Descamps (UGent) , Daisy Vanrompay (UGent) , Stefaan De Smedt (UGent) , Wim Van Den Broeck (UGent) , Bart Vandekerckhove (UGent) , Mathias Devreese (UGent) , Rein Verbeke (UGent) and Ine Lentacker (UGent)
- Organization
-
- Department of Pharmaceutics
- Department of Pathobiology, Pharmacology and Zoological Medicine
- Department of Morphology, Imaging, Orthopedics, Rehabilitation and Nutrition
- Department of Animal Sciences and Aquatic Ecology
- Ghent University Hospital
- Department of Electronics and information systems
- Department of Diagnostic Sciences
- Department of Head and Skin
- Project
-
- Understanding and modulating the pro-inflammatory activity of lipid nanoparticles (LNP) in the COVID-19 mRNA vaccines: towards the development of more effective LNP formulations.
- Exploration of an mRNA based nanovaccine platform and immunopeptidomics for the development of more effective tuberculosis vaccines.
- Exploring and advancing mRNA lipid nanoparticles for the in situ generation of CAR-Ms
- Immunopeptidomics-based Development of Next-Generation Bacterial mRNA Vaccines
- Vaccination with nucleoside-modified mRNA-ceramide lipoplexes: a phase I trial in stage IV lung carcinoma patients
- Further development of mRNA Galsomes as nanovaccines for cancer immunotherapy: combination with checkpoint inhibition and translation to the clinic.
- Smart design nanoParticles to Activate immune Responses against Cancer (SPARC)
- Accellerating towards clinical validation of Galsome nanovaccines
- Proteomics-derived epitopes for dramatically improved anticancer and antibacterial vaccine development
- High intensity focused ultrasound and mRNA nanomedicines: a new strategy to induce and boost anti-tumor immunity
- Abstract
- Galsome-NEO is a glycolipid-adjuvanted mRNA lipid nano-particle (LNP) cancer vaccine encoding neo-epitopes for evaluation in a phase 1 study in patients with non-small cell lung cancer. To assess the safety of Galsome-NEO, a repeated-dose toxicity study was conducted in Wistar Han rats involving three intramuscular doses of 30 mu g mRNA. A dose-escalation study in piglets tested three doses of 3, 15, and 100 mu g mRNA. Rats showed a pronounced pro-inflammatory response, evidenced by cytokine secretion and an acute phase reaction. Clinical findings included temporary local reactions (maximum grade 3), elevated temperatures, and weight loss. In pigs, all doses were well tolerated. Blood analysis showed elevated alkaline phosphatase and decreased thrombocytes in rats, while pigs had reduced reticulocyte counts. Histology revealed hepatocyte vacuolation in rats and immune infiltration at injection sites in both species. In rats, blood and histology alterations resolved 3 weeks post dosing, except for immune infiltration in the connective tissue at injection sites in two females. Galsomes with mRNA encoding the Chlamydia trachomatis major outer membrane protein induced T cell responses in pigs. Natural killer T cell activation was observed in both species. These findings align with the safety data for the COVID-19 mRNA vaccine, Comirnaty, and demonstrate Galsomes' potential in large animals.
- Keywords
- KILLER T-CELLS, IDENTIFICATION, INFECTION, ANEMIA
Downloads
-
publisher version.pdf
- full text (Published version)
- |
- open access
- |
- |
- 10.14 MB
Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01JVPG3QF3R3YNYT6RTBJ5P8AB
- MLA
- Meulewaeter, Sofie, et al. “Preclinical Toxicological Assessment of an α-Galactosylceramide-Adjuvanted MRNA Cancer Vaccine in Wistar Han Rats and Domestic Pigs.” MOLECULAR THERAPY METHODS & CLINICAL DEVELOPMENT, vol. 33, no. 2, 2025, doi:10.1016/j.omtm.2025.101493.
- APA
- Meulewaeter, S., De Velder, M., Reckelbus, D., Mwangi, K., Ehouarne, T., Aernout, I., … Lentacker, I. (2025). Preclinical toxicological assessment of an α-galactosylceramide-adjuvanted mRNA cancer vaccine in Wistar Han rats and domestic pigs. MOLECULAR THERAPY METHODS & CLINICAL DEVELOPMENT, 33(2). https://doi.org/10.1016/j.omtm.2025.101493
- Chicago author-date
- Meulewaeter, Sofie, Margo De Velder, Diethard Reckelbus, Kevin Mwangi, Thomas Ehouarne, Ilke Aernout, Yanou Engelen, et al. 2025. “Preclinical Toxicological Assessment of an α-Galactosylceramide-Adjuvanted MRNA Cancer Vaccine in Wistar Han Rats and Domestic Pigs.” MOLECULAR THERAPY METHODS & CLINICAL DEVELOPMENT 33 (2). https://doi.org/10.1016/j.omtm.2025.101493.
- Chicago author-date (all authors)
- Meulewaeter, Sofie, Margo De Velder, Diethard Reckelbus, Kevin Mwangi, Thomas Ehouarne, Ilke Aernout, Yanou Engelen, Fëllanza Halimi, Isis Van herteryck, Lobke De Bels, Valerie Redant, Louise De la Mane, Joline Ingels, Bo Coppens, Serge Van Calenbergh, Pieter Cornillie, Gabriële Holtappels, Benedicte Descamps, Daisy Vanrompay, Stefaan De Smedt, Wim Van Den Broeck, Bart Vandekerckhove, Mathias Devreese, Rein Verbeke, and Ine Lentacker. 2025. “Preclinical Toxicological Assessment of an α-Galactosylceramide-Adjuvanted MRNA Cancer Vaccine in Wistar Han Rats and Domestic Pigs.” MOLECULAR THERAPY METHODS & CLINICAL DEVELOPMENT 33 (2). doi:10.1016/j.omtm.2025.101493.
- Vancouver
- 1.Meulewaeter S, De Velder M, Reckelbus D, Mwangi K, Ehouarne T, Aernout I, et al. Preclinical toxicological assessment of an α-galactosylceramide-adjuvanted mRNA cancer vaccine in Wistar Han rats and domestic pigs. MOLECULAR THERAPY METHODS & CLINICAL DEVELOPMENT. 2025;33(2).
- IEEE
- [1]S. Meulewaeter et al., “Preclinical toxicological assessment of an α-galactosylceramide-adjuvanted mRNA cancer vaccine in Wistar Han rats and domestic pigs,” MOLECULAR THERAPY METHODS & CLINICAL DEVELOPMENT, vol. 33, no. 2, 2025.
@article{01JVPG3QF3R3YNYT6RTBJ5P8AB,
abstract = {{Galsome-NEO is a glycolipid-adjuvanted mRNA lipid nano-particle (LNP) cancer vaccine encoding neo-epitopes for evaluation in a phase 1 study in patients with non-small cell lung cancer. To assess the safety of Galsome-NEO, a repeated-dose toxicity study was conducted in Wistar Han rats involving three intramuscular doses of 30 mu g mRNA. A dose-escalation study in piglets tested three doses of 3, 15, and 100 mu g mRNA. Rats showed a pronounced pro-inflammatory response, evidenced by cytokine secretion and an acute phase reaction. Clinical findings included temporary local reactions (maximum grade 3), elevated temperatures, and weight loss. In pigs, all doses were well tolerated. Blood analysis showed elevated alkaline phosphatase and decreased thrombocytes in rats, while pigs had reduced reticulocyte counts. Histology revealed hepatocyte vacuolation in rats and immune infiltration at injection sites in both species. In rats, blood and histology alterations resolved 3 weeks post dosing, except for immune infiltration in the connective tissue at injection sites in two females. Galsomes with mRNA encoding the Chlamydia trachomatis major outer membrane protein induced T cell responses in pigs. Natural killer T cell activation was observed in both species. These findings align with the safety data for the COVID-19 mRNA vaccine, Comirnaty, and demonstrate Galsomes' potential in large animals.}},
articleno = {{101493}},
author = {{Meulewaeter, Sofie and De Velder, Margo and Reckelbus, Diethard and Mwangi, Kevin and Ehouarne, Thomas and Aernout, Ilke and Engelen, Yanou and Halimi, Fëllanza and Van herteryck, Isis and De Bels, Lobke and Redant, Valerie and De la Mane, Louise and Ingels, Joline and Coppens, Bo and Van Calenbergh, Serge and Cornillie, Pieter and Holtappels, Gabriële and Descamps, Benedicte and Vanrompay, Daisy and De Smedt, Stefaan and Van Den Broeck, Wim and Vandekerckhove, Bart and Devreese, Mathias and Verbeke, Rein and Lentacker, Ine}},
issn = {{2329-0501}},
journal = {{MOLECULAR THERAPY METHODS & CLINICAL DEVELOPMENT}},
keywords = {{KILLER T-CELLS,IDENTIFICATION,INFECTION,ANEMIA}},
language = {{eng}},
number = {{2}},
pages = {{17}},
title = {{Preclinical toxicological assessment of an α-galactosylceramide-adjuvanted mRNA cancer vaccine in Wistar Han rats and domestic pigs}},
url = {{http://doi.org/10.1016/j.omtm.2025.101493}},
volume = {{33}},
year = {{2025}},
}
- Altmetric
- View in Altmetric
- Web of Science
- Times cited: