Combination therapy with alisertib enhances the anti-tumor immunity induced by a liver cancer vaccine
Summary: Alisertib is a potent aurora A kinase inhibitor in clinical trials for cancer treatment, but its efficacy on cancer vaccines remains unclear. Here, we developed a DNA vaccine targeting glypican-3 (pGPC3) and evaluated its efficacy with alisertib in hepatocellular carcinoma (HCC) models. The...
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Elsevier
2025-04-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225003803 |
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| author | Fang Xue Jing Liu Jinyan Wu Xueer Li Ningning Zhu Shuting Tang Mengli Zhang Huan Duan Rui Wang Jing Zhang |
| author_facet | Fang Xue Jing Liu Jinyan Wu Xueer Li Ningning Zhu Shuting Tang Mengli Zhang Huan Duan Rui Wang Jing Zhang |
| author_sort | Fang Xue |
| collection | DOAJ |
| description | Summary: Alisertib is a potent aurora A kinase inhibitor in clinical trials for cancer treatment, but its efficacy on cancer vaccines remains unclear. Here, we developed a DNA vaccine targeting glypican-3 (pGPC3) and evaluated its efficacy with alisertib in hepatocellular carcinoma (HCC) models. The combination therapy of pGPC3 vaccine and alisertib significantly inhibited subcutaneous tumor growth, enhanced the induction and maturation of CD11c+ and CD8+CD11c+ dendritic cells (DCs), and expanded tumor-specific CD8+ T cell responses. CD8+ T cell depletion abolished the anti-tumor effects, underscoring the essential role of functional CD8+ T cell responses. Moreover, the combined treatment promoted memory CD8+ T cell induction, providing long-term protection. In liver orthotopic tumor models, the combination of pGPC3 vaccine and alisertib demonstrated potent therapeutic efficacy through CD8+ T cell responses. These results indicate that alisertib enhances the pGPC3 vaccine’s therapeutic effect, offering a promising strategy for HCC treatment. |
| format | Article |
| id | doaj-art-52841f5042f9407794b543539b87bfcc |
| institution | OA Journals |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-52841f5042f9407794b543539b87bfcc2025-08-20T02:10:02ZengElsevieriScience2589-00422025-04-0128411212010.1016/j.isci.2025.112120Combination therapy with alisertib enhances the anti-tumor immunity induced by a liver cancer vaccineFang Xue0Jing Liu1Jinyan Wu2Xueer Li3Ningning Zhu4Shuting Tang5Mengli Zhang6Huan Duan7Rui Wang8Jing Zhang9School of Nursing, Bengbu Medical University, Bengbu, Anhui 233030, China; Corresponding authorSurgical Oncology, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui 233004, ChinaSchool of Nursing, Bengbu Medical University, Bengbu, Anhui 233030, ChinaSchool of Nursing, Bengbu Medical University, Bengbu, Anhui 233030, ChinaSchool of Nursing, Bengbu Medical University, Bengbu, Anhui 233030, ChinaSchool of Nursing, Bengbu Medical University, Bengbu, Anhui 233030, ChinaSchool of Nursing, Bengbu Medical University, Bengbu, Anhui 233030, ChinaIntensive Care Unit, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui 233004, China; Corresponding authorDepartment of Medical Oncology, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui 233004, China; Anhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment, Bengbu Medical University, Bengbu 233004, Anhui, China; Corresponding authorSchool of Mental Health, Bengbu Medical University, Bengbu, Anhui 233030, China; Corresponding authorSummary: Alisertib is a potent aurora A kinase inhibitor in clinical trials for cancer treatment, but its efficacy on cancer vaccines remains unclear. Here, we developed a DNA vaccine targeting glypican-3 (pGPC3) and evaluated its efficacy with alisertib in hepatocellular carcinoma (HCC) models. The combination therapy of pGPC3 vaccine and alisertib significantly inhibited subcutaneous tumor growth, enhanced the induction and maturation of CD11c+ and CD8+CD11c+ dendritic cells (DCs), and expanded tumor-specific CD8+ T cell responses. CD8+ T cell depletion abolished the anti-tumor effects, underscoring the essential role of functional CD8+ T cell responses. Moreover, the combined treatment promoted memory CD8+ T cell induction, providing long-term protection. In liver orthotopic tumor models, the combination of pGPC3 vaccine and alisertib demonstrated potent therapeutic efficacy through CD8+ T cell responses. These results indicate that alisertib enhances the pGPC3 vaccine’s therapeutic effect, offering a promising strategy for HCC treatment.http://www.sciencedirect.com/science/article/pii/S2589004225003803Natural sciencesBiological sciencesImmunologySystems biologyCancer systems biology |
| spellingShingle | Fang Xue Jing Liu Jinyan Wu Xueer Li Ningning Zhu Shuting Tang Mengli Zhang Huan Duan Rui Wang Jing Zhang Combination therapy with alisertib enhances the anti-tumor immunity induced by a liver cancer vaccine iScience Natural sciences Biological sciences Immunology Systems biology Cancer systems biology |
| title | Combination therapy with alisertib enhances the anti-tumor immunity induced by a liver cancer vaccine |
| title_full | Combination therapy with alisertib enhances the anti-tumor immunity induced by a liver cancer vaccine |
| title_fullStr | Combination therapy with alisertib enhances the anti-tumor immunity induced by a liver cancer vaccine |
| title_full_unstemmed | Combination therapy with alisertib enhances the anti-tumor immunity induced by a liver cancer vaccine |
| title_short | Combination therapy with alisertib enhances the anti-tumor immunity induced by a liver cancer vaccine |
| title_sort | combination therapy with alisertib enhances the anti tumor immunity induced by a liver cancer vaccine |
| topic | Natural sciences Biological sciences Immunology Systems biology Cancer systems biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225003803 |
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