Glioblastoma refers to the most aggressive type of primary brain tumor that usually common amongst adults. At present, treatments for the diseases are only effective for a short period, after which it is known to reappear. The main cause for this is therapy-resistant Glioblastoma Stem Cells (GSCs). Thus, it is important to develop GSCs centric treatments against the disease. The best shot at achieving this is through immunotherapy that might help to improve the treatments present today; however, there has been less to no success in this sector till now.
A recent study might change this situation soon as it has published that GSCs can be targeted through NK (Natural Killer) Cells. The researchers showed evidence that NK cells could evade immune attack by releasing TFG-β signaling protein, thus blocking NK cell activity. The TFG-β receptor being killed within NK cells makes them resistant to immune suppression, leading them to exhibit anti-tumor activity. The new research is a huge breakthrough for Natural Killer Cells Therapeutics Market as it shows an approach that can help to eliminate tumor-regenerating GSCs. In fact, similar strategies could also benefit NK cell therapies in additional solid tumor forms as well.
To occur at the conclusion, the team first confirmed that NK cells were able to target GSCs in vitro. Non- edited NK cells received from healthy donors could eliminate patient-derived GSCs; however, in contrast, normal brain cells referred to as astrocytes remained unaffected.
Next, the team profiled TI-NK cells to understand their level of activity through single-cell RNA sequencing and protein markers. They promptly discovered that TI-NK cells displayed signals of immune suppression and inhibitory response relative to NK cells being isolated from the healthy donors’ blood. The research also clarified that in response to direct cell to cell contact with NK cells, GSCs produce TGF-β, which is a process being regulated by αν integrin proteins. The released TGF-βby GSCs activate the corresponding receptor “TGFBR2” on the NK cells so that anti-tumor activity can be blocked.
Through the use of a Vivo model of patient-derived GSCs, the research team demonstrated that combining donor-derived NK cells together with inhibitors that target either TGF-β receptors or αν integrins brought improvement in tumor control relative to unrelated control. Furthermore, results showed that the use of allogeneic NK cells along with TGFBR2 was genetically removed. The treatment altogether resulted in a considerable improvement of survival rate relative to unrelated controls.
The finding brought forth in the study suggests that a combinatorial approach of NK cell-based immunotherapy together with interruption of TGF-β signaling axis is needed to overcome the immune defenses of GSCs within the brain. In accordance with all the results, researchers stated that they would further work towards launching a clinical trial to evaluate the experimental approach as a prospective treatment against glioblastoma.