Researchers are investigating whether genetic engineering can restore the ability of natural killer cells to locate, enter and destroy certain tumours.
Natural killer (NK) cells may be an important new anti-cancer treatment option. Natural killer cells, as a part of a healthy immune system are able to effectively kill a wide range of tumour cells. Improved survival among renal cell carcinoma (RCC) patients, those afflicted with a cancer of the kidneys, is associated with higher numbers of NK NK cells gaining entry into tumours and subsequently destroying the cancerous cells.
As NK cells rely on the receipt of chemical signals to attract them to and cause them to enter their targets, their ability to display the proteins which receive chemical signals is paramount to their function. Many RCC tumours give off signal proteins that can be received by the receptor CXCR2, which NK cells naturally possess. When culturing NK cells to be used as a supplemental therapy for patients, however, CXCR2 levels are greatly reduced. Genetic engineering (the insertion, deletion, or alteration of specific segments of DNA) enables cultured NK cells to continue to produce CXCR2 and may help to correct the issue. Overcoming this limitation of NK therapy could improve survival among RCC patients and provide a therapeutic avenue for the treatment of patients with similar tumours.
In a recent Swedish study published in the Journal of ImmunoTherapy of Cancer, researchers investigated the ability of genetically engineered NK cells to locate, gain entry into, and destroy tumours that produce CXCR2 signal proteins. Blood and tumour samples were collected from 14 RCC patients who underwent whole or partial kidney removal. Patients’ NK cells were extracted from their blood samples and cultured for eight to ten days with or without one of two viral agents: one engineered to insert an overactive form of the CXCR2 gene, and one inserting a control gene for comparison.
The study findings suggest that genetically engineering NK cells to produce CXCR2 after culturing may be able to restore their ability to locate and enter tumours producing CXCR2 signal proteins. Further, it may be able to do so without impairing their ability to destroy the tumours. As the study’s experiments were conducted using cell culture techniques alone, further testing in live models will be required to confirm the findings of this study. This exciting study offers a promising new approach using genetic engineering to treating cancer.
Written by Raishard Haynes, MBS
Reference: Kremer, V. et al. (2017). Genetic engineering of human NK cells to express CXCR2 improves migration to renal cell carcinoma. JITC DOI 10.1186/s40425-017-0275-9