Preclinical toxicological assessment of an α-galactosylceramide-adjuvanted mRNA cancer vaccine in Wistar Han rats and domestic pigs
Galsome-NEO is a glycolipid-adjuvanted mRNA lipid nanoparticle (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 thre...
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Elsevier
2025-06-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050125000889 |
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| author | Sofie Meulewaeter Margo De Velder Diethard Reckelbus Kevin Mwangi Thomas Ehouarne Ilke Aernout Yanou Engelen Fellanza 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 C. De Smedt Wim Van den Broeck Bart Vandekerckhove Mathias Devreese Rein Verbeke Ine Lentacker |
| author_facet | Sofie Meulewaeter Margo De Velder Diethard Reckelbus Kevin Mwangi Thomas Ehouarne Ilke Aernout Yanou Engelen Fellanza 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 C. De Smedt Wim Van den Broeck Bart Vandekerckhove Mathias Devreese Rein Verbeke Ine Lentacker |
| author_sort | Sofie Meulewaeter |
| collection | DOAJ |
| description | Galsome-NEO is a glycolipid-adjuvanted mRNA lipid nanoparticle (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 μg mRNA. A dose-escalation study in piglets tested three doses of 3, 15, and 100 μg 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. |
| format | Article |
| id | doaj-art-2bf4e583878d433f86d31902e501974f |
| institution | OA Journals |
| issn | 2329-0501 |
| language | English |
| publishDate | 2025-06-01 |
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| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj-art-2bf4e583878d433f86d31902e501974f2025-08-20T02:32:20ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012025-06-0133210149310.1016/j.omtm.2025.101493Preclinical toxicological assessment of an α-galactosylceramide-adjuvanted mRNA cancer vaccine in Wistar Han rats and domestic pigsSofie Meulewaeter0Margo De Velder1Diethard Reckelbus2Kevin Mwangi3Thomas Ehouarne4Ilke Aernout5Yanou Engelen6Fellanza Halimi7Isis Van herteryck8Lobke De Bels9Valerie Redant10Louise De la Mane11Joline Ingels12Bo Coppens13Serge Van Calenbergh14Pieter Cornillie15Gabriële Holtappels16Benedicte Descamps17Daisy Vanrompay18Stefaan C. De Smedt19Wim Van den Broeck20Bart Vandekerckhove21Mathias Devreese22Rein Verbeke23Ine Lentacker24Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent University, 9000 Ghent, BelgiumGhent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent University, 9000 Ghent, BelgiumDepartment of Pathobiology, Pharmacology and Zoological Medicine, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, BelgiumGhent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent University, 9000 Ghent, BelgiumGhent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent University, 9000 Ghent, BelgiumGhent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent University, 9000 Ghent, BelgiumGhent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent University, 9000 Ghent, BelgiumDepartment of Pathobiology, Pharmacology and Zoological Medicine, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, BelgiumDepartment of Pathobiology, Pharmacology and Zoological Medicine, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, BelgiumDepartment of Morphology, Imaging, Orthopedics, Rehabilitation and Nutrition, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, BelgiumGMP Unit CellGenTherapies, Department of Human Body Material, Ghent University Hospital, Heymanslaan 10, 9000 Ghent, BelgiumGMP Unit CellGenTherapies, Department of Human Body Material, Ghent University Hospital, Heymanslaan 10, 9000 Ghent, BelgiumCancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; GMP Unit CellGenTherapies, Department of Human Body Material, Ghent University Hospital, Heymanslaan 10, 9000 Ghent, BelgiumGMP Unit CellGenTherapies, Department of Human Body Material, Ghent University Hospital, Heymanslaan 10, 9000 Ghent, BelgiumLaboratory of Medicinal Chemistry, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, BelgiumDepartment of Morphology, Imaging, Orthopedics, Rehabilitation and Nutrition, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, BelgiumUpper Airway Research Laboratory, Ghent University, 9000 Ghent, BelgiumCancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Department of Electronics and Information Systems, IbiTech-Medisip, Ghent University, 9000 Ghent, BelgiumDepartment of Animal Sciences and Aquatic Ecology, Faculty of Bioscience Engineering, Ghent University, 9000 Ghent, BelgiumGhent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent University, 9000 Ghent, BelgiumDepartment of Morphology, Imaging, Orthopedics, Rehabilitation and Nutrition, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, BelgiumCancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; GMP Unit CellGenTherapies, Department of Human Body Material, Ghent University Hospital, Heymanslaan 10, 9000 Ghent, BelgiumDepartment of Pathobiology, Pharmacology and Zoological Medicine, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, BelgiumGhent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Corresponding author: Rein Verbeke, Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium; Corresponding author: Ine Lentacker, Cancer Research Institute Ghent (CRIG), Ghent University Hospital, Ghent University, 9000 Ghent, Belgium.Galsome-NEO is a glycolipid-adjuvanted mRNA lipid nanoparticle (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 μg mRNA. A dose-escalation study in piglets tested three doses of 3, 15, and 100 μg 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.http://www.sciencedirect.com/science/article/pii/S2329050125000889lipid nanoparticlemRNA cancer vaccineNKT cellα-galactosylceramidetoxicology studypigs |
| spellingShingle | Sofie Meulewaeter Margo De Velder Diethard Reckelbus Kevin Mwangi Thomas Ehouarne Ilke Aernout Yanou Engelen Fellanza 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 C. De Smedt Wim Van den Broeck Bart Vandekerckhove Mathias Devreese Rein Verbeke Ine Lentacker Preclinical toxicological assessment of an α-galactosylceramide-adjuvanted mRNA cancer vaccine in Wistar Han rats and domestic pigs Molecular Therapy: Methods & Clinical Development lipid nanoparticle mRNA cancer vaccine NKT cell α-galactosylceramide toxicology study pigs |
| title | Preclinical toxicological assessment of an α-galactosylceramide-adjuvanted mRNA cancer vaccine in Wistar Han rats and domestic pigs |
| title_full | Preclinical toxicological assessment of an α-galactosylceramide-adjuvanted mRNA cancer vaccine in Wistar Han rats and domestic pigs |
| title_fullStr | Preclinical toxicological assessment of an α-galactosylceramide-adjuvanted mRNA cancer vaccine in Wistar Han rats and domestic pigs |
| title_full_unstemmed | Preclinical toxicological assessment of an α-galactosylceramide-adjuvanted mRNA cancer vaccine in Wistar Han rats and domestic pigs |
| title_short | Preclinical toxicological assessment of an α-galactosylceramide-adjuvanted mRNA cancer vaccine in Wistar Han rats and domestic pigs |
| title_sort | preclinical toxicological assessment of an α galactosylceramide adjuvanted mrna cancer vaccine in wistar han rats and domestic pigs |
| topic | lipid nanoparticle mRNA cancer vaccine NKT cell α-galactosylceramide toxicology study pigs |
| url | http://www.sciencedirect.com/science/article/pii/S2329050125000889 |
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