Scientists have used CRISPR/Cas9 gene editing technology to engineer cancer cells that seek out and kill their own kind, according to a study published yesterday in the journal Science Translational Medicine, covered in a Science News report.
Cancer cells in the bloodstream are naturally able to find other cancer cells, in order to find and return to a tumor. Taking advantage of this, scientists used gene editing to design these cells to release a protein that kills other tumor cells they encounter. In addition, the cells are engineered to self-destruct to prevent them from going on to create their own tumors.
Researchers have previously tried similar approaches, such as using cancer cells in the blood to bring cancer-killing viruses to the tumors themselves. However, the new approach takes advantage of the gene-editing technology to achieve a more sophisticated strategy, including features like self-destruction.
The surprising fact that cells return to their original site after metastasizing, discovered 12 years ago, is still one of the most hopeful prospects for cancer treatment. Several attempts to take advantage of this have fallen short, and the new study is itself quite preliminary.
The study was led by Khalid Shah, biologist and director of the Center for Stem Cell Therapeutics and Imaging at Brigham and Women’s Hospital. He says, since these cells “can track the original tumors, it is a matter of taming these cells to find the ultimate cure.”
Shah plans to stick with the approach, even founding a startup company to work on transforming the “rehoming” cells into cancer fighting agents.
In the new study, the researchers first looked for a protein that could kill a variety of different types of cancer cells, and would not harm healthy cells. They ultimately narrowed their search down to a protein called S-TRAIL. Then, two different strategies were tested. One used glioblastoma cells that were could survive the effects of the protein, and edited them to produce high quantities of S-TRAIL to kill other cancer cells.
The second approach used glioblastoma that were vulnerable to S-TRAIL, but took the extra step of removing the genes that cause the vulnerability, before adding genes to produce S-TRAIL.
Each approach has upsides and downsides.
The approach using initially S-TRAIL resistant cells could allow for ready-made cells to be stored and readily available in hospitals. But the other approach could be used to modify cells from each individual patient, offering a lower risk of rejection by the body. This approach, however, would require time for cells to be specially engineered, leaving terminal patients waiting.
In the study, both approaches reduced the size of tumors in mice, compared with those that had received neither treatment. Both groups of mice lived longer as well.