Kuehnoel, Caspar and Herbarth, Monique and Foell, Juergen and Staege, Martin S. and Kramm, Christof (2013) CD137 stimulation and p38 MAPK inhibition improve reactivity in an in vitro model of glioblastoma immunotherapy. CANCER IMMUNOLOGY IMMUNOTHERAPY, 62 (12). pp. 1797-1809. ISSN 0340-7004, 1432-0851
Full text not available from this repository. (Request a copy)Abstract
Dendritic cell vaccination has become an interesting option for cancer immunotherapy. Tumor-lysate-pulsed dendritic cells (DC) can prime na < ve T cells and induce the regression of established tumors including gliomas as shown in various animal models. Despite hopeful results even in clinical studies, the outcome for many patients is still unsatisfying. In the present study, we tested the combination of tumor-lysate-pulsed dendritic cells (TPDC) with a monoclonal antibody against CD137, a monoclonal antibody against CD25 (daclizumab) and a specific p38 mitogen-activated protein kinase (p38 MAPK) inhibitor (SB203580) for improving immunostimulation in an in vitro model of immunotherapy for human gliomas. We observed a higher secretion of interferon gamma by TPDC-primed peripheral blood mononuclear cells (PBMC) that were incubated with an antibody against CD137 or the p38 MAPK inhibitor. In addition, we observed higher specific lysis of tumor cells after incubation of PBMC with the p38 MAPK inhibitor or the anti-CD137 antibody. In contrast, incubation of TPDC-primed PBMC with the anti-CD25 antibody did enhance neither interferon gamma secretion nor cellular cytotoxicity. Cell depletion experiments demonstrated that the immune reaction induced by TPDC is strongly dependent on CD4-positive and CD8-positive cells. Incubation of DC during maturation and antigen loading with the anti-CD137 antibody did not enhance cytotoxicity and interferon gamma secretion in comparison with application of the anti-CD137 antibody during priming. In conclusion, our data suggest that p38 MAPK inhibition and anti-CD137 antibodies can enhance the immune response against glioblastoma cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACTIVATED PROTEIN-KINASE; DENDRITIC CELL VACCINATION; TUMOR-NECROSIS-FACTOR; CD4 T-CELLS; PHASE-I/II TRIAL; MALIGNANT GLIOMA; 4-1BB LIGAND; COSTIMULATORY MOLECULE; PROSTAGLANDIN E-2; SIGNALING PATHWAY; Glioblastoma; Dendritic cells; CD137; P38MAPK inhibitors; CD25 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Mar 2020 07:04 |
| Last Modified: | 25 Mar 2020 07:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15624 |
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