A lentiviral vector targeting a KRAS neoepitope for cancer immunotherapy
Abstract Mutated oncogenic Kirsten rat sarcoma virus (KRAS) antigen is expressed in a large variety of cancers, including pancreatic, colorectal, and pulmonary cancers. The oncogenic KRAS mutations cause malignancies and are usually ubiquitously expressed by all cells of a tumor. The KRAS amino acid...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-05134-6 |
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| author | Anastasia Goloudina Fabien Le Chevalier Pierre Authié Sylvain Ciret Kirill Nemirov Ingrid Fert Fanny Moncoq Benjamin Vesin Amandine Noirat Catherine Blanc Yu Wei Pierre Charneau Laleh Majlessi |
| author_facet | Anastasia Goloudina Fabien Le Chevalier Pierre Authié Sylvain Ciret Kirill Nemirov Ingrid Fert Fanny Moncoq Benjamin Vesin Amandine Noirat Catherine Blanc Yu Wei Pierre Charneau Laleh Majlessi |
| author_sort | Anastasia Goloudina |
| collection | DOAJ |
| description | Abstract Mutated oncogenic Kirsten rat sarcoma virus (KRAS) antigen is expressed in a large variety of cancers, including pancreatic, colorectal, and pulmonary cancers. The oncogenic KRAS mutations cause malignancies and are usually ubiquitously expressed by all cells of a tumor. The KRAS amino acid substitutions at the positions 12 or 13 are among the most frequent mutations in human cancers. Here, we developed immuno-oncotherapeutic non-integrative lentiviral vectors encoding a segment encompassing KRASG12D, either alone, or associated with antigen carriers. These carriers can improve the intracellular antigen routing to major histocompatibility complex presentation machineries or provide universal helper CD4+ epitopes. Immunotherapy with one of these vectors resulted in significant immune control of tumor growth in colorectal or pulmonary preclinical cancer models, in several murine genetic backgrounds. The antitumor effect was correlated with increased proportions of intra-tumoral hematopoietic cells and notably CD8+ T cells. Although this effect was partial, it was robust, reproducible and advantageously combinable with conventional chemotherapies and immunotherapies to improve antitumor protection. Therefore, this approach shows promise as an immuno-oncotherapy against KRAS-mediated malignant transformation. |
| format | Article |
| id | doaj-art-409d4972089e4bbb8536725bace33b7c |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-409d4972089e4bbb8536725bace33b7c2025-08-20T03:03:36ZengNature PortfolioScientific Reports2045-23222025-07-0115111710.1038/s41598-025-05134-6A lentiviral vector targeting a KRAS neoepitope for cancer immunotherapyAnastasia Goloudina0Fabien Le Chevalier1Pierre Authié2Sylvain Ciret3Kirill Nemirov4Ingrid Fert5Fanny Moncoq6Benjamin Vesin7Amandine Noirat8Catherine Blanc9Yu Wei10Pierre Charneau11Laleh Majlessi12Pasteur-TheraVectys Joint Laboratory, Institut Pasteur, Virology Department, Université de ParisPasteur-TheraVectys Joint Laboratory, Institut Pasteur, Virology Department, Université de ParisPasteur-TheraVectys Joint Laboratory, Institut Pasteur, Virology Department, Université de ParisPasteur-TheraVectys Joint Laboratory, Institut Pasteur, Virology Department, Université de ParisPasteur-TheraVectys Joint Laboratory, Institut Pasteur, Virology Department, Université de ParisPasteur-TheraVectys Joint Laboratory, Institut Pasteur, Virology Department, Université de ParisPasteur-TheraVectys Joint Laboratory, Institut Pasteur, Virology Department, Université de ParisPasteur-TheraVectys Joint Laboratory, Institut Pasteur, Virology Department, Université de ParisPasteur-TheraVectys Joint Laboratory, Institut Pasteur, Virology Department, Université de ParisPasteur-TheraVectys Joint Laboratory, Institut Pasteur, Virology Department, Université de ParisPasteur-TheraVectys Joint Laboratory, Institut Pasteur, Virology Department, Université de ParisPasteur-TheraVectys Joint Laboratory, Institut Pasteur, Virology Department, Université de ParisPasteur-TheraVectys Joint Laboratory, Institut Pasteur, Virology Department, Université de ParisAbstract Mutated oncogenic Kirsten rat sarcoma virus (KRAS) antigen is expressed in a large variety of cancers, including pancreatic, colorectal, and pulmonary cancers. The oncogenic KRAS mutations cause malignancies and are usually ubiquitously expressed by all cells of a tumor. The KRAS amino acid substitutions at the positions 12 or 13 are among the most frequent mutations in human cancers. Here, we developed immuno-oncotherapeutic non-integrative lentiviral vectors encoding a segment encompassing KRASG12D, either alone, or associated with antigen carriers. These carriers can improve the intracellular antigen routing to major histocompatibility complex presentation machineries or provide universal helper CD4+ epitopes. Immunotherapy with one of these vectors resulted in significant immune control of tumor growth in colorectal or pulmonary preclinical cancer models, in several murine genetic backgrounds. The antitumor effect was correlated with increased proportions of intra-tumoral hematopoietic cells and notably CD8+ T cells. Although this effect was partial, it was robust, reproducible and advantageously combinable with conventional chemotherapies and immunotherapies to improve antitumor protection. Therefore, this approach shows promise as an immuno-oncotherapy against KRAS-mediated malignant transformation.https://doi.org/10.1038/s41598-025-05134-6Cancer immunotherapyInhibition of tumor growthKRAS oncogenic mutationsKRASG12DLentiviral vectors |
| spellingShingle | Anastasia Goloudina Fabien Le Chevalier Pierre Authié Sylvain Ciret Kirill Nemirov Ingrid Fert Fanny Moncoq Benjamin Vesin Amandine Noirat Catherine Blanc Yu Wei Pierre Charneau Laleh Majlessi A lentiviral vector targeting a KRAS neoepitope for cancer immunotherapy Scientific Reports Cancer immunotherapy Inhibition of tumor growth KRAS oncogenic mutations KRASG12D Lentiviral vectors |
| title | A lentiviral vector targeting a KRAS neoepitope for cancer immunotherapy |
| title_full | A lentiviral vector targeting a KRAS neoepitope for cancer immunotherapy |
| title_fullStr | A lentiviral vector targeting a KRAS neoepitope for cancer immunotherapy |
| title_full_unstemmed | A lentiviral vector targeting a KRAS neoepitope for cancer immunotherapy |
| title_short | A lentiviral vector targeting a KRAS neoepitope for cancer immunotherapy |
| title_sort | lentiviral vector targeting a kras neoepitope for cancer immunotherapy |
| topic | Cancer immunotherapy Inhibition of tumor growth KRAS oncogenic mutations KRASG12D Lentiviral vectors |
| url | https://doi.org/10.1038/s41598-025-05134-6 |
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