Advances and challenges: dendritic cell vaccination strategies for glioblastoma

Abstract

Introduction Glioblastoma is the most common primary brain tumor in adults and prognosis remains poor with a median survival of approximately 15–17 months. This review provides an overview of recent advances in the field of glioblastoma immunotherapy. Areas covered Recent advances in dendritic cell vaccination immunotherapy are showing encouraging results in clinical trials and promise to extend patient survival. In this report we discuss current scientific knowledge regarding dendritic cell (DC) vaccines, including approaches to differentiating, priming, and injecting dendritic cells to achieve maximal anti-tumor efficacy in glioblastoma. These findings are compared to recently completed and currently ongoing glioblastoma clinical trials. Novel methods such as ‘fastDCs’ and vaccines targeting DCs in-vivo may offer more effective treatment when compared to traditional DC vaccines and have already entered the clinic. Expert Commentary Finally, we discuss the challenges of T-cell dysfunctions caused by glioblastoma immunosuppression and how they affect dendritic cell vaccinations approaches.

Challenging the indiscriminate use of temozolomide in pediatric high‐grade gliomas: A review of past, current, and emerging therapies

“…Evasion of the immune system constitutes one of the hallmarks of cancer . Cancer cells can escape immunological destruction by virtue of complex mechanisms, such as low immunogenicity, antigenic modulation, and immune suppression . Encouraging results using immunotherapies in melanoma and other cancers have demonstrated the staggering potential of redirecting the immune system, and research groups have strived toward incorporating immunotherapy into the armamentarium against HGG .…”

“…DCs constitute a link between the innate and adaptive immune responses and have been called the “sentinels” of the innate immune system because they look out for foreign antigens, particularly pathogen‐associated molecules. Then they take up, process, and present these antigens on MHC molecules to T and B lymphocytes . By doing so, they can trigger an adaptive immune response against those antigens .…”

The association between human cytomegalovirus and glioblastomas: a review

“…The idea of HCMV in GBM has led to potential immunotherapy targets for treatment of GBM. [73,74] A study conducted by Nair et al [75] evaluated whether T cells stimulated by HCMV pp65 RNA-transfected dendritic cells target and eliminate GBM tumor cells. The authors of this study concluded that HCMVspecific T cells can effectively target GBM tumor cells and their results support the rationale for the development of HCMV-directed immunotherapy in patients with GBM.…”

“…[75] As a result of this association and the potential therapeutic options, several groups are exploring novel approaches to developing GBMdirected immunotherapy and vaccines. [74] Potential HCMV proteins that are being investigated for the development of immunotherapy targets include immediate early 1 (IE1), phosphoprotein 65 (pp65), and glycoprotein B (gB). [74] …”

“…[74] Potential HCMV proteins that are being investigated for the development of immunotherapy targets include immediate early 1 (IE1), phosphoprotein 65 (pp65), and glycoprotein B (gB). [74] …”