Groundbreaking Experiment Designs Cancer Cells Attack to Their Own Tumors

Human T cell

Cancer cells circulating in the bloodstream have something of a homing instinct, able to find and return to the tumor where they originated. It turned out that some patients are refractory to treatment due to the fact that cancer cells have a particular protein on its surface.

Using gene editing, scientists have hoodwinked tumor cells into turning against their own kind, ScienceNews says.

"What takes months or even a year may now take a couple weeks using this new technology", Fred Ramsdell, vice president of research at the Parker Institute for Cancer Immunotherapy in San Francisco, where one of the authors of the study is a member, tells The New York Times. This study demonstrates self-tumor tropism of engineered cancer cells and their therapeutic potential when engineered with receptor self-targeted molecules, and it establishes a roadmap toward a safe clinical translation for different cancer types in primary, recurrent, and metastatic settings.

In a study published on Wednesday in the journal Science Translational Medicine, the team describes an innovative method of using the CRISPR gene-editing tool to design cancer cells that home in on the unsuspecting tumor to unleash a surprise attack.

With their inherent self-homing ability, the cells made their way back to the three tumors the study researchers were testing: primary glioblastoma, recurrent glioblastoma, and breast cancer that metastasized to the brain.

With the non-viral CRISPR technique, the UCSF team was able to quickly fix the IL2RA defect in the children's T cells, and to restore cellular signals that had been impaired by the mutations. That's because, as revolutionary as this method may be, there's still a lot that scientists don't know. To capitalize on that ability, researchers engineered these roving tumor cells to secrete a protein that triggers a death switch in resident tumor cells they encounter.

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"These cells were created to secrete death receptor-targeting ligands to which they were resistant to kill the main tumor but not destroy themselves", the authors explained in their paper.

"While we can never be absolutely certain that there are no off-target effects, there is a crucial difference in the nature of this type of therapy, where a new gene is introduced at a specific site in the genome", explained Roth. But the research is promising, nonetheless, and could revolutionize treatment for cancer and autoimmune diseases, including HIV and lupus.

CRISPR technique introduced by the UCSF team repaired the IL2RA defect which is found in the children's T-cells.

Roth said that because the new technique makes it possible to create viable custom T cell lines in a little over a week, it has already transformed the research environment in Marson's lab. Ideas for experiments that were previously deemed too hard or expensive because of the obstacles presented by viral vectors are now ripe for investigation. He is also part of the faculty at Harvard Medical School and Harvard Stem Cell Institute.

Marson attributes the new method's success to Roth's "absolute perseverance" in the face of the widespread beliefs that viral vectors were necessary and that only small pieces of DNA could be tolerated by T cells. Then these T cells are engineered artificially and then their genetic sequence will be able to fight more efficiently against cancer.



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