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Stem Cells in Focus

CRISPR, CAR-T, and Cancer

Researchers around the world have long sought effective treatments for cancer, and are now seeing therapeutic benefit with a new treatment, which is demonstrating better than imagined success in patients with blood cancer. The technology is called Chimeric Antigen Receptor T-cell therapy (CAR-T), which uses a patient’s own immune cells to fight cancer.

CAR-T immunotherapy involves genetically outfitting a patient’s immune cells with a new artificial gene, a chimeric antigen receptor (CAR), which allows the cells to recognize and attack specific cancer cells. The modified cells are infused back into the patient where they can target and fight the patient’s cancer.

This new therapy works well against B-cell acute lymphomblastic leukemia, a cancer of the blood system, which has led the U.S. Food and Drug Administration to expedite approval of the first CAR-T treatment for children and young adults. This is the first anti-cancer gene therapy available in the United States.

Challenges to Overcome

This treatment approach brings hope and high expectations that CAR-T may also work for other types of cancer. To get there, researchers will need to resolve certain obstacles associated with CAR-T, including further customization of the technology to recognize specific/other tumor types, and predicting and limiting cross-reactivity, where CAR-T immune cells start attacking healthy cells as well. Some of these obstacles may be resolved by capitalizing on a new technology called CRISPR/Cas9.

A New Research Tool

CRISPR/Cas9 has recently hit the headlines as a technology that is dramatically changing the way researchers are advancing science. This system, adapted from a naturally occurring process in bacteria, is being used to precisely and efficiently edit DNA. Cas9, a protein that acts as a molecular pair of scissors, is guided to a specific DNA sequence by an associated RNA molecule (a guide RNA). When Cas9 arrives at its target location on the DNA, it facilitates a change in the local genetic code, affecting the function of that gene. Because of the ease with which the CRISPR/Cas9 system can be applied, it has quickly become a robust tool for generating accurate genetic disease models in the laboratory and for identifying novel therapeutic targets in the clinic.

This technology is not without its challenges. Researchers are investigating how to reduce the risk of cutting DNA in the wrong places and how to make the targeting guide RNA more specific.

Yet, despite these challenges, the power of CRISPR/Cas9 is currently unmatched: it’s simple, cheap, fast, broadly applicable, and effective; projects that formerly required work by a team of researchers over the course of a year can now be easily done in a few days.

How can CRISPR/Cas9 Help CAR-T Immunotherapy?

Combining CAR-T immunotherapy and CRISPR/Cas9 may improve our chances of success for treating cancer and other genetic diseases in several ways. CRISPR/Cas9 may improve the engineering of T cells such that they carry multiple therapeutic features for either increasing specificity or suppressing side-effects, or both. CRISPR/Cas9 can also deliver the CAR gene to a very specific site within the T cell genome, which may reduce the risk of gene insertion at incorrect or undesired locations.

The future looks promising for CAR-T immunotherapy as a way to treat cancers, based on initial success with lymphomblastic leukemia. When combined with CRISPR/Cas9 technology, researchers may be able to create even more potent, customizable T cells to keep cancers and other genetic diseases at bay. These powerful tools are rapidly changing the way researchers do their work, and providing new and novel approaches to treatments for human disease.

 

 

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