mRNA-Based Therapy for Glioblastoma
Glioblastoma (GBM) is an aggressive primary brain tumor in adults. Due to its unique biological characteristics (such as diffusing invasiveness and high heterogeneity), the treatment of GBM in the oncological field has been a big challenge for decades. The treatment of GBM involves maximal surgical resection, chemotherapy, and radiotherapy. However, GBM shows the ability to resist conventional therapies. mRNA-based therapy as a novel modality holds potential for the treatment of GBM. On one hand, mRNA-based therapy has many superior features, which are suitable for addressing glioblastoma's variability and complexity. On another hand, synthetic anticancer mRNAs carried by various vehicles can cross biological barriers and specifically target glioblastoma by adding targeting molecules at certain levels. Here, we focus on the clinical therapeutic prospects of mRNA-based therapy for glioblastoma.
Creative Biogene is a forward-looking research institute as well as a leading custom service provider in mRNA-based drug research and development (R&D). Our team is experienced in the customized synthesis of mRNA, mRNA optimization, and mRNA delivery system development. We are committed to offering high-quality service and the best outcome for our customers from all over the world.
The challenges of GBM treatment
Glioblastoma (GBM) remains one of the most common and aggressive primary brain tumors with a poor prognosis. It is considered to arise from the neuroglial stem or progenitor cells and has been defined as a grade IV glioma by WHO. GBM has the highest recurrence rate (is recurrent in almost all patients) and remains an incurable disease with a high death rate (greater than 95% within 5 years of diagnosis).
The main reasons that GBM is challenging to treat, include,
- The blood-brain barrier (BBB) and brain-tumor barrier (BTB) as mechanical barriers, preventing drugs from entering gliomas' cells and protecting GBM from certain therapeutic agents.
- GBM has invasive growth property and restriction of surgical resection.
- The high heterogeneity of GBM.
mRNA-based therapy has special superiority for GBM treatment
Synthetic mRNAs can be delivered by nanoparticles, such as lipoplexes, polyplexes and exosomes, which are all able to cross natural barriers in the brain, including BBB and BTB. In addition, mRNA-based therapy is easy manipulation, short-term high-level expression, and has adaptive convertibility without genomic insertion risk. Due to its superior features, mRNA-based therapy has been intensively focused on cancer treatment, also making it a suitable therapeutic modality for dealing with the complexity and variability of GBM.
The highly specific targeting capability of mRNA-based therapy
The methods of targeting GBM with synthetic mRNA mainly include cellular level, exosome level and molecular level. Cell-mediated gene therapy is based on cells that have tumor-homing properties, including dendritic cells (DCs), NK cells, and mesenchymal stem cells (MSCs). These cells have superior advantages, such as the ability of tumor-directed migration and incorporation, easy acquisition and fast ex vivo expansion, as well as availability for autologous transplantation. The results of preclinical studies showed that the efficacy of cell-mediated and mRNA-based treatment of GBM is heterogeneous, and clinical trials in various stages are currently underway. Exosomes are derived from their parent cells. Exosome-mediated anticancer mRNA can target tumor cells via the targeting molecules in their membrane. Several GBM-specific targeting peptides that act on the different parts of tumor cells have been precisely studied. In addition, according to the expression of death receptors in tumor cells, tumor cells can be killed in a tumor-specific manner by the ultimate attack molecules.
A patient-tailored selection of mRNA administration method
The choice of administration route of mRNA to GBM patients depends on the general evaluation of the patient's glioma stage, grade, therapeutic history, and other parameters. In addition to intravenous infusion, the most practical administration method for various delivery forms of mRNA, there are other options, including cerebrospinal fluid infusion, local injection, interventional infusion and so on. Notably, it is reported that alternate use or a combination of different delivery methods and different mRNA content might be beneficial for GBM patients.
Proposed patient-tailored glioblastoma treatment with mRNA-based therapeutic modality. (Tang, X., et al, 2019)
Although the clinical trials of mRNA-based therapy in GBM are underway. Given the many superior features of mRNA-based therapy, we believe that this therapeutic modality holds great potential to be efficiently used for the treatment of patients with GBM. If you are interested in this area, please feel free to contact us. We look forward to providing services for your next project.
- Tang, X., et al. (2019). "Therapeutic prospects of mRNA-based gene therapy for glioblastoma." Frontiers in oncology, 9, 1208.