Scientists Have Tricked Cancer Cells Into Fighting Each Other Using CRISPR

T cells engineered using nonviral CRISPR technology to express green fluorescent protein

One method altered cells from the mice using the gene-editing technology CRISPR.

The researchers envision that the therapy could be translated to people by removing patients' tumors, engineering the cancer cells outside the body and then readministering the cells via a route that would depend on the type of the cancer and what stage it's in, they wrote.

The team used the CRISPR approach to introduce S-TRAIL to the cancer cells using two methods and found that in mice with primary brain cancer, recurrent brain cancer, and breast cancer that had metastasized to the brain, the engineered cells that were re-introduced to the body went directly to the tumors and also killed the cancer cells.

Taking healthy immune-boosting T cells from patients and engineering them to recognize and kill cancer is a well-established approach now, with the success of Gilead's Yescarta and Novartis' Kymriah. Results are published in Science Translational Medicine.

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Failure of chemotherapy to reach all cancer cells in a tumor is a major cause of poor treatment outcomes. "We think this has many implications and could be applicable across all cancer cell types". Harnessing this power could overcome drug delivery challenges, helping get therapeutics to tumor sites that may otherwise be hard to reach. In fact, study lead Khalid Shah, MS, PHD, and his team are planning to create a start-up that focuses on turning cancer cells into the tumors' own killers. The first were pre-engineered tumor cells that could be used off-the-shelf by matching them to patients' "HLA phenotypes", or the proteins that regulate their immune systems.

As with most preliminary cancer treatment research procedures, some lingering questions remain, most promptly what happens to the farther metastases after the tumor is destroyed, since scientists only know rehoming cells to make a one-way trip back to the tumor.

To test both approaches, the team used mouse models of primary and recurrent brain cancer and breast cancer that has spread to the brain. "In contrast, delivering the drug directly into the abdomen adjacent to ovarian tumors improved its target engagement, but this was still not sufficient to kill the cancer cells" says Erik Sahai, senior author of the paper and Group Leader at the Francis Crick Institute. The tumors in the mice that received the treatment reduced in size and they lived longer compared to the mice who did not receive the CRISPR cells. Engineered cells were equipped with a "kill switch" that could be activated after treatment - PET imaging showed that this kill switch worked to eliminate the cells.

"Our study demonstrates the therapeutic potential of using engineered tumor cells and their self-homing properties for developing receptor-targeted therapeutics for various cancers", Shah said, according to EurekAlert.

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