Therapeutic cell carriers: a potential road to cure glioma

Abstract

Many different experimental molecular therapeutic approaches have been evaluated in an attempt to treat brain cancer. However, despite the success of these experimental molecular therapies, research has shown that the specific and efficient delivery of therapeutic agents to tumor cells is a limitation. In this regard, cell carrier systems have garnered significant attraction due to their capacity to be loaded with therapeutic agents and carry them specifically to tumor sites. Furthermore, cell carriers can be genetically modified to express therapeutic agents that can directly eradicate cancerous cells or can modulate tumor microenvironments. This review describes the current state of cell carriers, their use as vehicles for the delivery of therapeutic agents to brain tumors, and future directions that will help overcome the present obstacles to cell carrier mediated therapy for brain cancer.

Keywords::

• brain cancer
• cell carriers
• gene therapy
• glioblastoma multiforme
• glioma
• induced progenitor cells
• mesenchymal stem cells
• neural stem cells
• oncolytic virotherapy
• tumor-tropism

Acknowledgements

This work is supported by NIH grants R01CA122930, R01CA138587, R01NS077388 and U01NS069997.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Even with surgical, chemotherapy and radiotherapy treatments, the life expectancy for patients with a primary brain tumor, like glioma, is about 12–18 months.

• One of the biggest challenges to gene therapy techniques is the specific delivery of the therapeutic agent to the target site.

• Cell carriers can act as drug factories while they seek out multiple, distributed tumor foci and specifically deliver their therapeutic payload.

• Cell carriers can be modified and loaded with oncolytic viral agents, shielding the virus from the immune system and improving the viral delivery to the tumor site.

• Cytotoxic or immunomodulatory genes can be directly added to the cell carrier, which will deliver this therapy to the target site.

• There are obstacles to overcome before cell carrier delivered therapy can be a safe clinical option for patients. The administered cell carriers must not elicit an immune response or result in tumorigenesis while they efficiently migrate to the tumor.

• Modifications can be made to cell carriers so that they exhibit enhanced tumor tropism, extended life spans and therefore a larger therapeutic benefit.

• Future research is needed to examine what mediates the tumor tropism of these cells, as well as identify which cell carrier is most efficacious for the treatment of different tumors.