TY  - JOUR
A1  - Eyrich, Matthias
A1  - Rachor, Johannes
A1  - Schreiber, Susanne C.
A1  - Wölfl, Matthias
A1  - Schlegel, Paul G.
T1  - Dendritic cell vaccination in pediatric gliomas: lessons learnt and future perspectives
JF  - Frontiers in Pediatrics
N2  - Immunotherapy of malignant gliomas with autologous dendritic cells (DCs) in addition to surgery and radiochemotherapy has been a focus of intense research during the past decade. Since both children and adults are affected by this highly aggressive brain tumor, 10–15% of the several hundred vaccinated patients represent children, making pediatric glioma patients the largest uniform pediatric vaccination cohort so far. In general, DC vaccination in malignant gliomas has been shown to be safe and several studies with a non-vaccinated control group could clearly demonstrate a survival benefit for the vaccinated patients. Interestingly, children and adolescents below 21 years of age seem to benefit even more than adult patients. This review summarizes the findings of the 25 clinical trials published so far and gives a perspective how DC vaccination could be implemented as part of multimodal therapeutic strategies in the near future.
KW  - pediatrics
KW  - malignant glioma
KW  - DC vaccination
KW  - clinical trial
KW  - immunotherapy
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96937
ER  - 
TY  - JOUR
A1  - Gierlich, Philipp
A1  - Lex, Veronika
A1  - Technau, Antje
A1  - Keupp, Anne
A1  - Morper, Lorenz
A1  - Glunz, Amelie
A1  - Sennholz, Hanno
A1  - Rachor, Johannes
A1  - Sauer, Sascha
A1  - Marcu, Ana
A1  - Grigoleit, Götz Ulrich
A1  - Wölfl, Matthias
A1  - Schlegel, Paul G.
A1  - Eyrich, Matthias
T1  - Prostaglandin  E\(_2\) in a TLR3‑ and 7/8‑agonist‑based DC maturation cocktail generates mature, cytokine‑producing, migratory DCs but impairs antigen cross‑presentation to  CD8\(^+\) T cells
JF  - Cancer Immunology, Immunotherapy
N2  - Mature dendritic cells (DCs) represent cellular adjuvants for optimal antigen presentation in cancer vaccines. Recently, a combination of prostaglandin  E\(_2\) (PGE\(_2\)) with Toll-like receptor agonists (TLR-P) was proposed as a new standard to generate superior cytokine-producing DCs with high migratory capacity. Here, we compare TLR-P DCs with conventional DCs matured only with the proinflammatory cytokines TNFα and IL-1ß (CDCs), focussing on the interaction of resulting DCs with  CD8\(^+\) T-cells. TLR-P matured DCs showed elevated expression of activation markers such as CD80 and CD83 compared to CDCs, together with a significantly higher migration capacity. Secretion of IL-6, IL-8, IL-10, and IL-12 was highest after 16 h in TLR-P DCs, and only TLR-P DCs secreted active IL-12p70. TLR-P DCs as well as CDCs successfully primed multifunctional CD8\(^+\) T-cells from naïve precursors specific for the peptide antigens Melan-A, NLGN4X, and PTP with comparable priming efficacy and T-cell receptor avidity.  CD8\(^+\) T-cells primed by TLR-P DCs showed significantly elevated expression of the integrin VLA-4 and a trend for higher T-cell numbers after expansion. In contrast, TLR-P DCs displayed a substantially reduced capability to cross-present CMVpp65 protein antigen to pp65-specific T cells, an effect that was dose-dependent on  PGE2 during DC maturation and reproducible with several responder T-cell lines. In conclu-sion, TLR-P matured DCs might be optimal presenters of antigens not requiring processing such as short peptides. However,  PGE\(_2\) seems less favorable for maturation of DCs intended to process and cross-present more complex vaccine antigens such as lysates, proteins or long peptides.
KW  - dendritic cells
KW  - cancer vaccines
KW  - prostaglandin  E2
KW  - TLR agonists
KW  - tumor-specific  CD8+ T cells
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232311
SN  - 0340-7004
VL  - 69
ER  -