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Dendritic-cell- and peptide-based vaccination strategies for glioma

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Abstract

Despite advances in radiation and chemotherapy along with surgical resectioning, the prognosis of patients with malignant glioma is poor. Therefore, the development of a new treatment modality is extremely important. There are increasing reports demonstrating that systemic immunotherapy using dendritic cells and peptide is capable of inducing an antiglioma response. This review highlights dendritic-cell- and peptide-based immunotherapy for glioma patients. Dendritic-cell- and peptide-based immunotherapy strategies appear promising as an approach to successfully induce an antitumor immune response and increase survival in patients with glioma. Dendritic cell- and peptide-based therapy of glioma seems to be safe and without major side effects. There are several types of glioma; so to achieve effective therapy, it may be necessary to evaluate the molecular genetic abnormalities in individual patient tumors and design novel immunotherapeutic strategies based on the pharmacogenomic findings. Here, in this review, recent advances in dendritic-cell- and peptide-based immunotherapy approaches for patients with gliomas are discussed.

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  1. Research Center of Innovative Cancer Therapy, Kurume University School of Medicine, Asahimachi 67, Kurume, Fukuoka, 830-0011, Japan

    Ryuya Yamanaka

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Comments

Patrick Roth, Michael Weller, Zurich, Switzerland

Malignant gliomas remain a major challenge in the field of neuro-oncology. Despite multimodal therapy, including surgical resection, radiotherapy, and chemotherapy along with the identification of predictive markers for response to treatment such as the epigenetic silencing of the O6-methylguanine-DNA methyltransferase (MGMT) gene, the prognosis for the affected patients has only been slightly improved. Novel therapeutic approaches include targeted therapies such as the administration of small molecules or monoclonal antibodies that inhibit their target specifically. Exquisite specificity is also one of the hallmarks of the immune system which is therefore regarded as a potential and extremely precise weapon against tumors. The various alterations that are expressed by malignant glioma cells may, in general, provide antigenic targets for recognition by the immune system. However, as proven by the clinical course, gliomas hide from the immune system and further avoid immune attack by various immunosuppressive mechanisms. Harnessing the immune system against these tumors by overcoming such obstacles may therefore be a promising therapeutic approach.

Here, the author provides a detailed overview on dendritic cell (DC)- and peptide-based immunotherapeutic strategies, important pitfalls, and an overview on future directions. DC and peptide vaccination have entered the clinic within the last 10 years. Until today, the general experience with such therapeutic approaches has shown excellent tolerability and immune responses against the vaccine but only few favorable clinical responses. The disappointing results of these studies have probably several reasons, including a lack of immunogenicity of tumor cells, inadequate adjuvants, or too low levels of antigens of value. Additionally, there might be tumor cells that are particularly resistant to an attack by the immune system. With the identification of tumor-initiating cells with stem cell properties within gliomas, a population of cells has been identified that may contribute to this immunoresistance. These “stem-like cells” may also explain the inevitable recurrence of gliomas and define these cells as novel targets to overcome the resistance to conventional and immunotherapy in this disease. Based on these novel insights of glioma biology, future immunotherapeutic strategies against malignant gliomas targeting specifically glioma-initiating cells might be more successful than previous approaches. The optimization of vaccination protocols includes further steps such as the selection of “personalized” peptides and a modulation of tumor-associated immunosuppression. Given these considerations, one can optimistically await future immunotherapeutic clinical trials for glioma patients.

Jun Yoshida, Nagoya, Japan

Malignant gliomas remain untreatable and lethal despite the extensive application of surgical excision and additional radiotherapy and/or chemotherapy.

Therefore, various immunotherapy approaches are being explored and appear promising as new therapeutic methods. Immunotherapy for human tumors has been proposed based on the finding that CD8+ cytotoxic T lymphocytes (CTLs) are capable of effective recognition and destruction of tumor cells.

Consequently, much attention has been paid to the identification and characterization of glioma-associated antigens that may elicit strong and highly glioma-specific immune reactions. This review article focuses on DC-based immunotherapeutic approaches. It was of particular interest to read the “Dendritic cells in tumor immunology” section, in which the author describes recent findings on the role of DCs on tumor immunology.

Recently, new subsets of DCs with diverse function have been identified.

Not only that glioma-associated antigens or peptides that elicit stronger immune response should be identified, also, more comprehensive understanding of DCs should be crucial in order to improve the efficacy of immunotherapy toward gliomas.

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Yamanaka, R. Dendritic-cell- and peptide-based vaccination strategies for glioma. Neurosurg Rev 32, 265–273 (2009). https://doi.org/10.1007/s10143-009-0189-1

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