Prostaglandin E 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.

Mature dendritic cells (DCs) represent cellular adjuvants for optimal antigen presentation in cancer vaccines. Recently, a combination of prostaglandin E (PGE) 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.

High-grade glioma associated immunosuppression does not prevent immune responses induced by therapeutic vaccines in combination with T depletion.

High-grade gliomas (HGG) exert systemic immunosuppression, which is of particular importance as immunotherapeutic strategies such as therapeutic vaccines are increasingly used to treat HGGs. In a first cohort of 61 HGG patients we evaluated a panel of 30 hematological and 34 plasma biomarkers. Then, we investigated in a second cohort of 11 relapsed HGG patients receiving immunomodulation with metronomic cyclophosphamide upfront to a DC-based vaccine whether immune abnormalities persisted and whether they hampered induction of IFNγ T-cell responses.

Immunotherapy in atypical teratoid-rhabdoid tumors: Data from a survey of the HGG-Immuno Group.

Background Aims: Atypical rhabdoid/teratoid tumors (AT/RT) are the most common brain tumors in infants and associated with a dismal prognosis. Although intensification of first-line therapy has resulted in improvement of overall survival, novel treatment strategies are needed. Because immunotherapy has resulted in remarkable results in several adult tumor entities, incorporation of immunotherapy into AT/RT treatment offers a novel alternative.

Development and validation of a fully GMP-compliant production process of autologous, tumor-lysate-pulsed dendritic cells.

Background And Aims: One of the major challenges of dendritic cell (DC) vaccination is the establishment of harmonized DC production protocols. Here, we report the transfer and validation of a successfully used open DC manufacturing method into a closed system, good manufacturing practice (GMP)-compatible protocol.

Methods: All production steps (lysate generation, monocyte selection, DC culture and cryopreservation) were standardized and validated.

Dendritic cell vaccination in pediatric gliomas: lessons learnt and future perspectives.

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.

Stimulating surface molecules, Th1-polarizing cytokines, proven trafficking--a new protocol for the generation of clinical-grade dendritic cells.

Background Aims: Dendritic cells (DC) have been vigorously investigated as an immunological basis for therapeutic vaccination against cancer and infections, even among patients after allogeneic stem cell transplantation.

Methods: Effective induction of cell-mediated immunity strongly depends on the ability of DC to (i) migrate to the draining lymphoid organs mediated by chemokine receptors, (ii) prime T cells through high expression of costimulatory molecules and major histocompatibility complexes and (iii) secret Th1-polarizing cytokines such as Interleukin-12 (IL-12). However, there is no protocol to generate fully matured and functional DC according to methodical requirements of current good manufacturing practice (CGMP) guidelines.