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Introduction: Prospective double-blind placebo-controlled randomized clinical trials (RCTs) are considered standard for the proof of the efficacy of oncologic therapies. Molecular methods have provided new insights into tumor biology and led to the development of targeted therapies. Due to the increasing complexity of molecular tumor characteristics and of the individuality of specific anti-tumor immune reactivity, RCTs are unfortunately only of limited use., Areas Covered: The historical methods of drug research and approval and the related practices of reimbursement by statutory and private health insurance companies are being questioned. New, innovative methods for the documentation of evidence in personalized medicine will be addressed. Possible perspectives and new approaches are discussed, in particular with regard to glioblastoma., Expert Opinion: Highly specialized translational oncology groups like the IOZK can contribute to medical progress and quick transfer 'from bench to bedside.' Their contribution should be acknowledged and taken into account more strongly in the development of guidelines and the reimbursement of therapy costs. Methodological plurality should be encouraged.

Dendritic cell (DC)-based immunotherapy has yielded promising results against high-grade glioma (HGG). However, the efficacy of DC vaccines is abated by HGG-induced immunosuppression and lack of attention toward the immunogenicity of the tumor lysate/cells used for pulsing DCs. A literature analysis of DC vaccination clinical trials in HGG patients delineated the following two most predominantly applied methods for tumor lysate preparation: freeze-thaw (FT)-induced necrosis or FT-necrosis followed by X-ray irradiation. However, from the available clinical evidence, it is unclear which of both methodologies has superior immunogenic potential. Using an orthotopic HGG murine model (GL261-C57BL/6), we observed that prophylactic vaccination with DCs pulsed with irradiated FT-necrotic cells (compared to FT-necrotic cells only) prolonged overall survival by increasing tumor rejection in glioma-challenged mice. This was associated, both in prophylactic and curative vaccination setups, with an increase in brain-infiltrating Th1 cells and cytotoxic T lymphocytes (CTL), paralleled by a reduced accumulation of regulatory T cells, tumor-associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC). Further analysis showed that irradiation treatment of FT-necrotic cells considerably increased the levels of carbonylated proteins - a surrogate-marker of oxidation-associated molecular patterns (OAMPs). Through further application of antioxidants and hydrogen peroxide, we found a striking correlation between the amount of lysate-associated protein carbonylation/OAMPs and DC vaccine-mediated tumor rejection capacity thereby suggesting for the first time a role for protein carbonylation/OAMPs in at least partially mediating antitumor immunity. Together, these data strongly advocate the use of protein oxidation-inducing modalities like irradiation for increasing the immunogenicity of tumor lysate/cells used for pulsing DC vaccines.

Pelvic gynecological malignancies account for 6% of all cancers. In the relapsed state, classical treatments are limited. There is an urgent need for new and personalized treatment. Wilms' tumor gene 1 (WT1) is the most important tumor-associated antigen. Although highly present in gynecological tumors, active immunotherapy against it is still underexplored. This review gives an insight into the importance of WT1 in pelvic gynecological malignancies and the first taken steps into the world of WT1 immunotherapy.

Uterine cancer is the most common pelvic gynecological malignancy. Uterine sarcomas and relapsed uterine carcinomas have limited treatment options. The search for new therapies is urgent. Dendritic cell (DC) immunotherapy holds much promise, though has been poorly explored in uterine cancer. This commentary gives an insight in existing DC immunotherapy studies in uterine cancer and summarizes the possibilities and the importance of the loading of tumor antigens onto DC and their subsequent maturation. However, the sole application of DC immunotherapy to target uterine cancer will be insufficient because of tumor-induced immunosuppression, which will hamper the establishment of an effective anti-tumor immune response. The authors give an overview on the limited existing immunosuppressive data and propose a novel approach on DC immunotherapy in uterine cancer.

Worldwide, 80% of patients with ovarian cancer die of the disease. New treatments for this aggressive disease are therefore being intensively searched. Although dendritic cell-based vaccines against gynecological malignancies are in their infancy, this immunotherapeutic approach holds much promise. Here, we present our view on an optimal dendritic cell-based immunotherapeutic strategy against ovarian cancer.

The prognosis of patients diagnosed with high-grade glioma continues to be dismal in spite of multimodal treatment. Active specific immunotherapy by means of dendritic cell vaccination is considered to be a new promising concept that aims at generating an anti-tumoral immune response. However, it is now widely accepted that the success of immunotherapeutic strategies to promote tumor regression will rely not only on enhancing the effector arm of the immune response but also on downregulation of the counteracting tolerogenic signals. In this article, we summarize evidence that galectin-1, an evolutionarily conserved glycan-binding protein that is abundantly expressed in high-grade glioma, is an important player in glioma-mediated immune escape.