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Boston researchers re-engineer cancer cells to fight off 'their own kind'

14 July 2018

The team is using CRISPR gene editing to modify cancer cells so they can home in on tumors and deliver therapies to them. In the meantime, scientists are seeking approval from the U.S. Food and Drug Administration to use the repaired T cells to treat the three children. The cancer-fighting cancer cells also have a built-in suicide switch - so the weaponized cells self-destruct before they can start tumors of their own. According to the study, when these altered cells were returned to the body, they showed the potential to boost immune systems so they could fight cancer on their own.

"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. Even when available, viral vectors are far from ideal, because they insert genes haphazardly into cellular genomes, which can damage existing healthy genes or leave newly introduced genes ungoverned by the regulatory mechanisms which ensure that cells function normally.

The technology "really opens up the ability for us, as a community, to think about very creative and potentially unique ways to activate a T cell", Ramsdell tells The Post. "Our nonviral editing approach efficiently inserts new DNA sequences at specific sites".

To validate these findings, Roth directed CRISPR to label an array of different T cell proteins with green fluorescent protein (GFP), and the outcome was highly specific, with very low levels of "off-target" effects: each subcellular structure Roth's CRISPR templates had been created to tag with GFP - and no others - glowed green under the microscope. Genetic adjustment is another tool in use and it has been showing some promising new results.

In the first example, Roth and colleagues used T cells provided to the Marson lab by Yale School of Medicine's Kevan Herold, MD. But the research is promising, nonetheless, and could revolutionize treatment for cancer and autoimmune diseases, including HIV and lupus.

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T-cells are the part of immune cells and are formed by the process of hematopoiesis.

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.

"Our study demonstrates the therapeutic potential of using engineered tumor cells and their self-homing properties for developing receptor-targeted therapeutics for various cancers", added Shah. This is a rare disease and called as a genetic form of autoimmunity.

The two approaches were tested in mouse models that suffered from primary brain cancer, recurrent brain cancer, and breast cancer that had spread to the brain.

Cancer cells circulating in the bloodstream have something of a homing instinct, able to find and return to the tumor where they originated. A breakthrough in genetic engineering have managed to do thanks to the technique CRISPR. 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. "With this new technique we can cut and paste into a specified place, rewriting a specific page in the genome sequence".

Boston researchers re-engineer cancer cells to fight off 'their own kind'