Glioblastoma (GBM) represents the most common and aggressive primary
brain tumor with a 5-years survival rate lower than 10%. GBM worldwide incidence is
about two to three per 100000 adults per year, and the standard treatment encompasses
surgical debulking with subsequent radiation therapy and concomitant chemotherapy.
Given its heterogenicity, its intracranial location and the onset of multidrug resistance
mechanisms, new tailored approaches, such as immunotherapy and drug delivery
systems, have recently gained increasing interest. In recent years, tumor
microenvironment exploration has revealed that immune response evasion is one of the
crucial GBM diagnostic hallmarks. Since this discovery, the possibility to reverse
tumor-mediated immunosuppression has received increasing attention, changing the
paradigm of cancer treatment from chemotherapy to immunotherapy. On the other
hand, the blood-brain barrier (BBB) represents the main challenge in developing
therapeutics for central nervous system (CNS) tumors; for instance, 100% of large
molecules and 98% of small molecules fail to achieve sufficient therapeutic doses at
the brain. To this purpose, nanotechnology-based drug delivery systems represent
promising platforms to improve drug bioavailability, reduce side effects and allow the
co-delivery of multiple drugs to the target cells.
This chapter gives an overview of current innovative approaches to GBM focusing on
the therapeutic benefit of immunotherapeutic agents and drug delivery systems. In
particular, we aim to provide a summary of the recent clinical trials using
immunomodulator, immune checkpoint inhibitors (ICIs), i.e. monoclonal antibodies
(mAbs) blocking cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and
programmed cell death-1 (PD-1/PD-L1a), vaccination therapy. Although ICIs and
vaccines have shown limited efficacy when used as monotherapy, promising results
have been reported for their combination with immune adjuvants, such as chemo, radio- and photodynamic therapies, suggesting an emerging strategy for a more
successful antitumoral immune response. With this chapter, we aim to provide an
overview of the state-of-the-art and future perspective of GBM treatment, mainly
addressed to pharmaceutical students and researchers in the field of clinical drug
research.
Keywords: Blood-Brain Barrier (BBB), Blood-Brain Tumor Barrier (BBTB),
Clinical trials, Combination approach, Drug Resistance, Glioblastoma, Immune
Checkpoint Inhibitors (ICIs), Immunotherapy, Long-term Immune Memory,
Nanocarriers, Nanomedicine, Vaccine.