Glioblastoma is the most aggressive and fast-growing type of brain cancer. Prognosis is poor and the average length of survival for patients is only around eight months. There is currently no cure, and treatment – such as radiation, chemotherapy, or debulking of the tumor – serves to prolong life rather than save it. Researchers from the German Cancer Research Center and the University Medical Center Mannheim hope to change this, turning to transgenic T cells to treat glioblastoma in a recent study (1).
Glioblastoma patients were inoculated with a tumor-associated antigen harbored in NLGN4X – a protein involved with the formation of synapses which is typically overexpressed in human gliomas. Blood samples from vaccinated individuals were collected, and NLGN4X-activated T cells were isolated to access the specific T cell receptor. The gene responsible for coding the receptor was also isolated so that sufficient quantities of T cells with identical specificity could be used for cell therapy.
In a culture dish, the team proved these human T cells effectively lysed NLGN4X-expressing tumor cells. The method was also tested in glioma-bearing mice, where transgenic NLGN4X-specific human T cells were administered through cerebral ventricle injection. The diseased mice had a response rate of 44.4 percent, compared with zero percent in control groups.
Lukas Bunse, co-author of the study, wrote about the benefits of transgenic T cells over CAR T cells: “A major limitation of CAR T cells is that the extracellular antibody domain of CARs is only able to bind extracellular surface antigens [...] TCR-transgenic T cells, in contrast, are able to specifically target intracellularly expressed antigens.”
Overall, the study showed how promising transgenic T cells are as a therapeutic strategy to target glioblastoma-associated antigens.
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References
- C Krämer et al., Neuro Oncol [Online ahead of print] (2023). PMID: 37715782