Anti-GD2 antibody and Vorinostat immunocombination therapy is highly effective in an aggressive orthotopic neuroblastoma model
Neuroblastoma is a childhood malignancy and in the majority of patients, the primary tumor arises in one of the adrenal glands. Neuroblastoma cells highly express the disialoganglioside GD2, which is the primary target for the development of neuroblastoma immunotherapy. Anti-GD2 mAbs have shown clin...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-01-01
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| Series: | OncoImmunology |
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| Online Access: | http://dx.doi.org/10.1080/2162402X.2020.1817653 |
| _version_ | 1818721644258000896 |
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| author | Renske J. E. van den Bijgaart Michiel Kroesen Ingrid C. Brok Daphne Reijnen Melissa Wassink Louis Boon Peter M. Hoogerbrugge Gosse J Adema |
| author_facet | Renske J. E. van den Bijgaart Michiel Kroesen Ingrid C. Brok Daphne Reijnen Melissa Wassink Louis Boon Peter M. Hoogerbrugge Gosse J Adema |
| author_sort | Renske J. E. van den Bijgaart |
| collection | DOAJ |
| description | Neuroblastoma is a childhood malignancy and in the majority of patients, the primary tumor arises in one of the adrenal glands. Neuroblastoma cells highly express the disialoganglioside GD2, which is the primary target for the development of neuroblastoma immunotherapy. Anti-GD2 mAbs have shown clinical efficacy and are integrated into standard treatment for high-risk neuroblastoma patients. We previously reported synergy between the HDAC inhibitor Vorinostat and anti-GD2 mAbs in a heterotopic, subcutaneous growing neuroblastoma model. Additionally, we have previously developed an orthotopic intra-adrenal neuroblastoma model showing more aggressive tumor growth. Here, we report that anti-GD2 mAb and Vorinostat immunocombination therapy is even more effective in suppressing neuroblastoma growth in the aggressive orthotopic model, resulting in increased animal survival. Intra-adrenal tumors from mice treated with Vorinostat were highly infiltrated with myeloid cells, including macrophages, displaying increased MHCII and Fc-receptor expression. Collectively, these data provide a strong rationale for clinical testing of anti-GD2 mAbs with concomitant Vorinostat in neuroblastoma patients. |
| first_indexed | 2024-12-17T20:42:00Z |
| format | Article |
| id | doaj.art-1e1ec552e48646038e1f6be9869c3425 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-17T20:42:00Z |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-1e1ec552e48646038e1f6be9869c34252022-12-21T21:33:16ZengTaylor & Francis GroupOncoImmunology2162-402X2020-01-019110.1080/2162402X.2020.18176531817653Anti-GD2 antibody and Vorinostat immunocombination therapy is highly effective in an aggressive orthotopic neuroblastoma modelRenske J. E. van den Bijgaart0Michiel Kroesen1Ingrid C. Brok2Daphne Reijnen3Melissa Wassink4Louis Boon5Peter M. Hoogerbrugge6Gosse J Adema7Radboud University Medical CenterHolland Proton Therapy CenterRadboud University Medical CenterRadboud University Medical CenterRadboud University Medical CenterBiocerosPrincess Máxima Center for Pediatric OncologyRadboud University Medical CenterNeuroblastoma is a childhood malignancy and in the majority of patients, the primary tumor arises in one of the adrenal glands. Neuroblastoma cells highly express the disialoganglioside GD2, which is the primary target for the development of neuroblastoma immunotherapy. Anti-GD2 mAbs have shown clinical efficacy and are integrated into standard treatment for high-risk neuroblastoma patients. We previously reported synergy between the HDAC inhibitor Vorinostat and anti-GD2 mAbs in a heterotopic, subcutaneous growing neuroblastoma model. Additionally, we have previously developed an orthotopic intra-adrenal neuroblastoma model showing more aggressive tumor growth. Here, we report that anti-GD2 mAb and Vorinostat immunocombination therapy is even more effective in suppressing neuroblastoma growth in the aggressive orthotopic model, resulting in increased animal survival. Intra-adrenal tumors from mice treated with Vorinostat were highly infiltrated with myeloid cells, including macrophages, displaying increased MHCII and Fc-receptor expression. Collectively, these data provide a strong rationale for clinical testing of anti-GD2 mAbs with concomitant Vorinostat in neuroblastoma patients.http://dx.doi.org/10.1080/2162402X.2020.1817653neuroblastomaorthotopicimmunotherapyanti-gd2 mab therapyhistone deacetylase inhibitor |
| spellingShingle | Renske J. E. van den Bijgaart Michiel Kroesen Ingrid C. Brok Daphne Reijnen Melissa Wassink Louis Boon Peter M. Hoogerbrugge Gosse J Adema Anti-GD2 antibody and Vorinostat immunocombination therapy is highly effective in an aggressive orthotopic neuroblastoma model OncoImmunology neuroblastoma orthotopic immunotherapy anti-gd2 mab therapy histone deacetylase inhibitor |
| title | Anti-GD2 antibody and Vorinostat immunocombination therapy is highly effective in an aggressive orthotopic neuroblastoma model |
| title_full | Anti-GD2 antibody and Vorinostat immunocombination therapy is highly effective in an aggressive orthotopic neuroblastoma model |
| title_fullStr | Anti-GD2 antibody and Vorinostat immunocombination therapy is highly effective in an aggressive orthotopic neuroblastoma model |
| title_full_unstemmed | Anti-GD2 antibody and Vorinostat immunocombination therapy is highly effective in an aggressive orthotopic neuroblastoma model |
| title_short | Anti-GD2 antibody and Vorinostat immunocombination therapy is highly effective in an aggressive orthotopic neuroblastoma model |
| title_sort | anti gd2 antibody and vorinostat immunocombination therapy is highly effective in an aggressive orthotopic neuroblastoma model |
| topic | neuroblastoma orthotopic immunotherapy anti-gd2 mab therapy histone deacetylase inhibitor |
| url | http://dx.doi.org/10.1080/2162402X.2020.1817653 |
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