Glioblastoma (GBM) is the most common, aggressive, and neurological destructive primary brain tumour in adults, among the most lethal human malignancies. An estimated 8-10,000 cases of GBM are diagnosed (in both sexes) every year. The current treatment includes safe maximal surgical resection of the accessible tumour followed by radiotherapy and chemotherapy combined with corticosteroids after three to four weeks. However, this approach is highly invasive, and not always applicable (40% of patients have unresectable GBM). Despite the invasive treatment, the prognosis for GBM is very poor and the patient's median survival is 14.6 months. Reasons behind the inefficacy of therapy against GBM reside in its anatomical location (the blood-brain barrier (BBB) precludes the passage of the majority of chemotherapy agents to the brain) and its aggressive tumour immune microenvironment (TIME) that plays a significant role in GBM progression and diffusion by stimulating angiogenesis and cell migration. In this context, immunotherapy has emerged as a potentially efficient means to treat cancers by turning the immune system against tumour cells. Notable progress in the field of immunotherapy has been made, particularly with the use of tumor vaccines; especially peptide vaccines and cell-based vaccines such as dendritic cell vaccines and tumor cell vaccines. Despite the impressive progression of immunotherapeutics and vaccination strategies, GBM remains a "cold," resistant, and deadly cancer. One solution is to break with traditional drug development paradigms and engineer the delivery of immunotherapeutics to target tissues (GBM or lymph nodes) or cell types to control the timing/location of immunomodulation. To achieve this goal, nanomedicine-based approaches offer a means to increase immunotherapeutic efficacy.
Due to the high incidence of GBM in European citizens and the observation of 70% of cases in patients between 45 and 70 years, the need for new therapeutic approaches will have significant social, clinical, and economic relevance and impact. Furthermore, the socioeconomic burden of GBM will be reduced by diminishing side effects and treatment costs. We also speculate that our strategy can be translated into other cancer types lacking immunotherapy approaches (e.g. brain metastasis and pediatric tumours). We developed the proposed research project with the knowledge that innovation alone is not sufficient for the development of an original scientific project; we must also answer patient needs and impact lifestyles.
