Samenvatting
Background: Electroporation of dendritic cells (DC) with mRNA encoding CD40 ligand, a constitutively active TLR4 and CD70 improves the immunostimulatory capacity of autologous DC. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibits costimulatory signalling provided by DC to activate T lymphocytes.
Methods: Ipilimumab, a fully human anti-CTLA-4 antibody, was added to cultures of sorted CD8+ and CD4+CD25- T-cells with autologous DC (isolated from advanced melanoma patients) and anti-CD3 beads. T-cell proliferation and cytokine secretion were examined thereafter.
Results: TriMix-DC were fully matured in the presence of increasing concentrations of ipilimumab. There was no influence on the DC cytokine secretion (IL-10 and IL-12p70). TriMix-DC significantly enhanced the cytokine secretion (IFN-gamma, TNF-alpha and IL-2) and chemokine secretion (MIP-1beta) of both CD8+ and CD4+CD25- T cells as compared to immature DC and DC matured with a cytokine mix. There was no difference in the proliferative capacity of CD8+ and CD4+ CD25- T cells stimulated with autologous DC and anti-CD3 beads in the presence of ipilimumab as compared to isotype control (up to a concentration of 50 ?g/ml). In the presence of ipilimumab, the IL-2 secretion of CD4+ CD25- T cells stimulated with TriMix-DC was significantly increased. In contrast, the IL-2 secretion of sorted CD8+ T cells stimulated with TriMix-DC was not altered.
Conclusion: CTLA-4 blockade with ipilimumab enhances the IL-2 production of CD4+ CD25- T cells stimulated with autologous TriMix-DC in vitro and may enhance the efficacy of TriMix-DC-immunotherapy in melanoma patients.
Methods: Ipilimumab, a fully human anti-CTLA-4 antibody, was added to cultures of sorted CD8+ and CD4+CD25- T-cells with autologous DC (isolated from advanced melanoma patients) and anti-CD3 beads. T-cell proliferation and cytokine secretion were examined thereafter.
Results: TriMix-DC were fully matured in the presence of increasing concentrations of ipilimumab. There was no influence on the DC cytokine secretion (IL-10 and IL-12p70). TriMix-DC significantly enhanced the cytokine secretion (IFN-gamma, TNF-alpha and IL-2) and chemokine secretion (MIP-1beta) of both CD8+ and CD4+CD25- T cells as compared to immature DC and DC matured with a cytokine mix. There was no difference in the proliferative capacity of CD8+ and CD4+ CD25- T cells stimulated with autologous DC and anti-CD3 beads in the presence of ipilimumab as compared to isotype control (up to a concentration of 50 ?g/ml). In the presence of ipilimumab, the IL-2 secretion of CD4+ CD25- T cells stimulated with TriMix-DC was significantly increased. In contrast, the IL-2 secretion of sorted CD8+ T cells stimulated with TriMix-DC was not altered.
Conclusion: CTLA-4 blockade with ipilimumab enhances the IL-2 production of CD4+ CD25- T cells stimulated with autologous TriMix-DC in vitro and may enhance the efficacy of TriMix-DC-immunotherapy in melanoma patients.
| Originele taal-2 | English |
|---|---|
| Titel | CIMT Annual Meeting |
| Status | Published - 2013 |
| Evenement | Unknown - Duur: 1 jan 2013 → … |
Conference
| Conference | Unknown |
|---|---|
| Periode | 1/01/13 → … |