Advanced Cell Therapies for Glioblastoma

Abstract

The sheer ubiquity of Gioblastoma (GBM) cases would lead you to believe that there should have been many opportunities for the discovery of treatments to successfully render it into remission. Unfortunately, its persistent commonality is due in large part to the fact that it is the most treatment-resistant tumors in adults. That completely changes the treatment plan of attack. Long established and accepted treatment therapies such as surgical resection, radiation, and aggressive chemotherapy, (and any combination thereof) have only confirmed that the disease lives up to its treatment-resistant reputation. To add to the seemingly insurmountable task of finding a cure, GBM has also proven to be a very stubborn and formidable opponent to newer immunotherapies. Across the board, regardless of the therapy combination, the five-year survival rate of GBM patients is still very poor at a heartbreaking 5.6%. Obviously, the present situation cannot be tolerated or deemed acceptable. The grave situation calls for researchers to be more innovative and find more efficient strategies to discover new and successful strategies to treat GBM. Inspired by researchers worldwide attempting to control GBM, we provide in this review a comprehensive overview of the many diverse cell therapies currently being used to treat GBM. An overview of the treatments include: CAR T cells, CAR NK cells, gamma-delta T cells, NKT cells, dendritic cells, macrophages, as well stem cell-based strategies. To give you the complete picture, we will discuss the efficacy, safety, and developmental stages, the mechanisms of action and the challenges of each of these therapies and detail their potential to be the next-generation immunotherapeutic to eliminate this dreadful disease.

Hallmarks of the Tumour Microenvironment of Gliomas and Its Interaction with Emerging Immunotherapy Modalities

“…CAR NK-cell therapy is another potential therapeutic avenue for glioblastoma. Unlike T cells, NK cells, as mentioned before, are part of the innate immune system [73]. They directly recognise and eliminate cancer cells without prior antigen experience via an antigenindependent mechanism [74].…”

“…By switching from conventional CAR T-cell to NK signalling domains, CAR NK cells exhibit improved tumour-killing function. The targets being explored for CAR NK cells in glioblastoma are like those of CAR T-cell therapies [73].…”

“…However, technical challenges in CAR-NK development, large-scale manufacturing, and need to create bespoke molecules remain major limiting factors for all types of CAR therapies. This warrants the optimisation of gene-modification and -expansion methods for successful clinical trials of CAR NK-cell and T-cell therapies for glioblastoma [73].…”

A novel prognostic risk-scoring system based on m5C methylation regulator-mediated patterns for glioma patients

“…High-grade glioma patients have an abysmal prognosis even when undergoing a combination of therapies, including operation, radiation, chemotherapy, hormonotherapy, and immunotherapy. 10 , 11 The significant heterogeneity of gliomas in terms of the composition of the immune microenvironment and gene mutations could account for their varied biological behavior. 12 Impaired regulation of the immune response and immune evasion could cause tumorigenesis, invasion, and metastasis.…”

Biological roles of SLC16A1-AS1 lncRNA and its clinical impacts in tumors

“…In glioblastoma, a notably aggressive form of brain tumor [ 109 – 111 ], SLC16A1-AS1 has been identified as playing a pivotal oncogenic role, as elucidated by in vitro studies. Research by Jin et al [ 93 ] revealed that in glioblastoma cells, the lncRNA SLC16A1-AS1 regulates both mature and premature forms of miR-1269.…”