Engineered cancer cells (green) shown returning to the original glioblastoma tumor (red) in a mouse brain (Credit: Brigham and Women’s Hospital)

Cancer cells circulating in the bloodstream are being used to create an army of cancer-killing cells using gene-editing.

Scientists are taking advantage of the “self-homing” abilities of cancer cells that have left the original tumour. The study, reported in Science Translational Medicine,demonstrates how tumour cells can be engineered using CRISPR technologies to secrete proteins called S-TRAIL that trigger “death receptors” on the original cancer mass without killing themselves. The ability to resist the effects of the death receptor trigger was also engineered using CRISPR-Cas9.

Since rehoming tumor cells “can track the original tumors, it is a matter of taming these cells to find the ultimate cure” said Biologist Khalid Shah, director of the Center for Stem Cell Therapeutics and Imaging at Brigham and Women’s Hospital and the leader of the study.

Shah’s also planning a startup company to turn rehoming cells into cancer killers and said that in the year since the new study was submitted to the journal, he and his colleagues have obtained more data on how well CRISPR’d rehoming tumor cells can attack cancer: “We’re in it for the long term.”

The ability to resist the effects of the death receptor trigger was engineered using CRISPR-Cas9 using two different approaches. One uses cancer cells taken from the body and engineers them to be resistant before being reinserted back into the body and the other use standard cells that are resistant.

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Each approach has pros and cons, says Shah.

In a clinical setting — still a long way off for this research — using cells that aren’t yet resistant to S-TRAIL could be “a little bit cumbersome,” Shah says. It would enable doctors to collect patients’ own cancer cells, and then turn them into a weapon targeted against people’s specific cancer. But the wait time for that special cellular engineering might make the option a no-go for very sick patients.

The other approach, built with standard cells that are already resistant to S-TRAIL, could be stockpiled in hospitals for quick and easy access. But because those cells would be foreign to a patient, there would be a greater risk that the body would reject them.

Some key questions still need to be addressed, especially when we consider that more than 90% of cancer deaths are caused by metastases and not the solid tumour mass, where this treatment seems to be focusing.

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Shah and his team did give the engineered cells a kill switch so that administering a simple drug would kill them, hopefully preventing the continued spread of cancer following its fight against its home base. This addresses the concern of the CRISPR’d cells initiating new tumours.

The work tested the efficacy and safety of the method in mouse models of primary, recurrent, and metastatic tumors but it remains to be seen how well that would work in people.