A novel method for efficient generation of antigen-specific effector T-cells using dendritic cells transduced with recombinant adeno-associated virus and p38 kinase blockade
Abstract Background The inefficacy of standard therapeutic strategies for ovarian cancer is reflected by the enduring poor prognosis of this malignancy. Due to the potential for exquisite specificity, sensitivity and long-term memory, immunotherapy offers an alternative modality for durable control...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-12-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-019-02163-4 |
| _version_ | 1828946662687506432 |
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| author | Leonardo Mirandola Maurizio Chiriva-Internati Robert Bresalier Lucia Piccotti Fabio Grizzi Francesco M. Marincola |
| author_facet | Leonardo Mirandola Maurizio Chiriva-Internati Robert Bresalier Lucia Piccotti Fabio Grizzi Francesco M. Marincola |
| author_sort | Leonardo Mirandola |
| collection | DOAJ |
| description | Abstract Background The inefficacy of standard therapeutic strategies for ovarian cancer is reflected by the enduring poor prognosis of this malignancy. Due to the potential for exquisite specificity, sensitivity and long-term memory, immunotherapy offers an alternative modality for durable control of the disease, provided appropriate antigens can be identified and presented in the right context. Methods We tested a novel dendritic cell vaccine formulation to reprogram autologous antigen-specific T-cells in vitro, in vivo in a murine model of ovarian cancer, and ex vivo using human cells from patients. Results We show that dendritic cells (DCs) treated with a p38 MAPK inhibitor and transduced with a recombinant adenovirus associated vector (AAV) expressing Sperm protein (Sp) 17 are highly effective in generating antigen-specific T-cell cytotoxic response against ovarian cancer cells. Additionally, these DCs enhanced the differentiation of effector T-cells while reducing the frequency of Foxp3+ T-reg cells in vitro. Conclusions This work provides a rationale for translation of pharmacologically reprogrammed DCs into clinical trials for prevention of tumor recurrence and progression in high-risk ovarian cancer patients. |
| first_indexed | 2024-12-14T05:14:59Z |
| format | Article |
| id | doaj.art-2a9800ce847b4a94b8b8510398ff19a9 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-14T05:14:59Z |
| publishDate | 2019-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-2a9800ce847b4a94b8b8510398ff19a92022-12-21T23:15:51ZengBMCJournal of Translational Medicine1479-58762019-12-011711910.1186/s12967-019-02163-4A novel method for efficient generation of antigen-specific effector T-cells using dendritic cells transduced with recombinant adeno-associated virus and p38 kinase blockadeLeonardo Mirandola0Maurizio Chiriva-Internati1Robert Bresalier2Lucia Piccotti3Fabio Grizzi4Francesco M. Marincola5Kiromic, IncKiromic, IncDivision of Internal Medicine, Department of Gastroenterology Hepatology and Nutrition, The University of Texas MD Anderson Cancer CenterKiromic, IncDepartment of Immunology and Inflammation, Humanitas Clinical and Research CenterKiromic, IncAbstract Background The inefficacy of standard therapeutic strategies for ovarian cancer is reflected by the enduring poor prognosis of this malignancy. Due to the potential for exquisite specificity, sensitivity and long-term memory, immunotherapy offers an alternative modality for durable control of the disease, provided appropriate antigens can be identified and presented in the right context. Methods We tested a novel dendritic cell vaccine formulation to reprogram autologous antigen-specific T-cells in vitro, in vivo in a murine model of ovarian cancer, and ex vivo using human cells from patients. Results We show that dendritic cells (DCs) treated with a p38 MAPK inhibitor and transduced with a recombinant adenovirus associated vector (AAV) expressing Sperm protein (Sp) 17 are highly effective in generating antigen-specific T-cell cytotoxic response against ovarian cancer cells. Additionally, these DCs enhanced the differentiation of effector T-cells while reducing the frequency of Foxp3+ T-reg cells in vitro. Conclusions This work provides a rationale for translation of pharmacologically reprogrammed DCs into clinical trials for prevention of tumor recurrence and progression in high-risk ovarian cancer patients.https://doi.org/10.1186/s12967-019-02163-4Ovarian cancer vaccineDendritic cellsp38 MAP kinaseT-regs |
| spellingShingle | Leonardo Mirandola Maurizio Chiriva-Internati Robert Bresalier Lucia Piccotti Fabio Grizzi Francesco M. Marincola A novel method for efficient generation of antigen-specific effector T-cells using dendritic cells transduced with recombinant adeno-associated virus and p38 kinase blockade Journal of Translational Medicine Ovarian cancer vaccine Dendritic cells p38 MAP kinase T-regs |
| title | A novel method for efficient generation of antigen-specific effector T-cells using dendritic cells transduced with recombinant adeno-associated virus and p38 kinase blockade |
| title_full | A novel method for efficient generation of antigen-specific effector T-cells using dendritic cells transduced with recombinant adeno-associated virus and p38 kinase blockade |
| title_fullStr | A novel method for efficient generation of antigen-specific effector T-cells using dendritic cells transduced with recombinant adeno-associated virus and p38 kinase blockade |
| title_full_unstemmed | A novel method for efficient generation of antigen-specific effector T-cells using dendritic cells transduced with recombinant adeno-associated virus and p38 kinase blockade |
| title_short | A novel method for efficient generation of antigen-specific effector T-cells using dendritic cells transduced with recombinant adeno-associated virus and p38 kinase blockade |
| title_sort | novel method for efficient generation of antigen specific effector t cells using dendritic cells transduced with recombinant adeno associated virus and p38 kinase blockade |
| topic | Ovarian cancer vaccine Dendritic cells p38 MAP kinase T-regs |
| url | https://doi.org/10.1186/s12967-019-02163-4 |
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