Published: Sat, July 14, 2018
Medicine | By Douglas Stevenson

Scientists Use Gene Editing To Trick Cancer Cells Into Killing Each Other

Scientists Use Gene Editing To Trick Cancer Cells Into Killing Each Other

"We think this has many implications and could be applicable across all cancer cell types". It relies on electroporation, a process in which an electrical field is applied to cells to make their membranes temporarily more permeable. To achieve this, the researchers inserted new genes into T cells taken from patients.

"Now we're off to the races on all these fronts", he added.

"With our technique, we show it is possible to reverse-engineer a patient's own cancer cells and use them to treat cancer", said co-author Khalid Shah, Ph.D., director of the Center for Stem Cell Therapeutics and Imaging in the BWH Department of Neurosurgery.

The researchers developed two different types of cells.

After using the different variable for certain years, The UCSF researchers got to know that when CRISPR, DNA, and T-cells are mixed and exposed to the electrical field then T-cells will be able to take in the elements and new DNA sequence will be integrated precisely. Now they are focusing to experiment it in humans. These limitations, which could potentially lead to serious side effects, have been cause for concern in both gene therapy and cell therapies such as CAR-T-based immunotherapy. Scientists took advantage of this trait to use CRISPR-engineered cells to turn against their own kind.

The new method, described in the July 11, 2018 issue of Nature, offers a robust molecular "cut and paste" system to rewrite genome sequences in human T cells. We created therapeutic tumor cells expressing ligands specific to primary and recurrent tumor sites (receptor self-targeted tumor cells) and extensively characterized two different approaches using (i) therapy-resistant cancer cells, engineered with secretable death receptor-targeting ligands for "off-the-shelf" therapy in primary tumor settings, and (ii) therapy-sensitive cancer cells, which were CRISPR-engineered to knock out therapy-specific cell surface receptors before engineering with receptor self-targeted ligands and reapplied in autologous models of recurrent or metastatic disease. But the research is promising, nonetheless, and could revolutionize treatment for cancer and autoimmune diseases, including HIV and lupus.

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.

Cancer cells have a "self-homing" ability that allows them to travel through the bloodstream and seek out other cancerous cells of the same type, originating from the same tumor. A breakthrough in genetic engineering have managed to do thanks to the technique CRISPR. But the problem is that T-cells which are engineered by the help of a virus is really expensive and painstaking process.

"This strategy of replacing the T cell receptor can be generalized to any T cell receptor", said senior study author Dr. Alex Marson, associate professor of microbiology and immunology at UCSF, in a news release. "By optimizing each of these parameters and putting the best conditions together he was able to see this astounding result".

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