CAR T cells more powerful when built with CRISPR, researchers find

February 22, 2017, Memorial Sloan Kettering Cancer Center

Researchers from Memorial Sloan Kettering Cancer Center (MSK) have harnessed the power of CRISPR/Cas9 to create more-potent chimeric antigen receptor (CAR) T cells that enhance tumor rejection in mice. The unexpected findings, published in Nature on February 22, uncover facets of CAR immunobiology and underscore the potential of CRISPR/Cas9 genome editing to advance immunotherapies for cancer.

CRISPR is a genome-editing tool that enables scientists to cut and manipulate a cell's DNA with high precision. In the Nature paper, MSK investigators show that CRISPR technology can deliver the CAR gene to a very specific location in the genome of the T cell. This precise approach creates CAR T with more stamina—they can kill for longer because they are less prone to becoming exhausted. This could eventually lead to safer, more effective use of this powerful form of immunotherapy in patients.

"Cancer cells are relentless in their attempt to evade treatment, so we need CAR T cells that can match and outlast them," explained Michel Sadelain, MD, PhD, senior author on the Nature paper and Director of the Center for Cell Engineering and the Gene Transfer and Gene Expression Laboratory at MSK. "This new discovery shows that we may be able to harness the power of genome editing to give these 'living therapies' a built-in boost. We are eager to continue exploring how genome-editing technology could give us the next generation of CAR T cell therapy."

Some of the first clinical trials using CRISPR technology are currently in the planning stages. Dr. Sadelain and his team aim to eventually explore the safety and efficacy of these CRISPR-built CAR T cells in a trial. Currently, CAR T cells are usually made using a retroviral or lentiviral technology to deliver the CAR gene into the T cells. This delivery method results in the CAR gene being inserted at random into the genome of the recipient cells, which can result in unwanted genetic side effects.

Explore further: Modifying fat content in soybean oil with the molecular scissors Cpf1

More information: Justin Eyquem et al, Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection, Nature (2017). DOI: 10.1038/nature21405

Related Stories

Modifying fat content in soybean oil with the molecular scissors Cpf1

February 16, 2017
A team from the Center for Genome Engineering, within the Institute for Basic Research (IBS), succeeded in editing two genes that contribute to the fat contents of soybean oil using the new CRISPR-Cpf1 technology: an alternative ...

Tuberculosis-resistant cows developed for the first time using CRISPR technology

January 31, 2017
CRISPR/Cas9 gene-editing technology has been used for the first time to successfully produce live cows with increased resistance to bovine tuberculosis, reports new research published in the open access journal Genome Biology.

Watching gene editing at work to develop precision therapies

January 24, 2017
University of Wisconsin-Madison engineers have developed methods to observe gene editing in action, and they're putting those capabilities to work to improve genetic engineering techniques.

Overcoming hurdles in CRISPR gene editing to improve treatment

February 7, 2017
More and more scientists are using the powerful new gene-editing tool known as CRISPR/Cas9, a technology isolated from bacteria, that holds promise for new treatment of such genetic diseases as cystic fibrosis, muscular dystrophy ...

Genome surgery with CRISPR-Cas9 to prevent blindness

February 16, 2017
It is estimated that almost one in every ten people over 65 has some signs of age-related macular degeneration (AMD), and its prevalence is likely to increase as a consequence of the aging population. AMD is a form of blindness, ...

CRISPR meets single-cell sequencing in new screening method

January 19, 2017
Genome editing using CRISPR/Cas9 "gene scissors" is a powerful tool for biological discovery and for identifying novel drug targets. In pooled CRISPR screens, a large number of cells are edited simultaneously using CRISPR ...

Recommended for you

Precision neuroengineering enables reproduction of complex brain-like functions in vitro

November 14, 2018
One of the most important and surprising traits of the brain is its ability to dynamically reconfigure the connections to process and respond properly to stimuli. Researchers from Tohoku University (Sendai, Japan) and the ...

Gene mutation found to cause macrocephaly and intellectual deficits

November 13, 2018
The absence of one copy of a single gene in the brain causes a rare, as-yet-unnamed neurological disorder, according to new research that builds on decades of work by a University at Buffalo biochemist and his colleagues.

Can scientists change mucus to make it easier to clear, limiting harm to lungs?

November 12, 2018
For healthy people, mucus is our friend. It traps potential pathogens so our airways can dispatch nasty bugs before they cause harm to our lungs. But for people with conditions such as cystic fibrosis (CF) and chronic obstructive ...

Scientists uncover new gatekeeper function of anti-aging molecule

November 12, 2018
The protein klotho has been shown to promote longevity and counteract aging-related impairments. Having more klotho seems to allow for longer and healthier lives, whereas a depletion of this molecule accelerates aging and ...

Mutations, CRISPR, and the biology behind movement disorders

November 12, 2018
Scientists at the RIKEN Center for Brain Science (CBS) in Japan have discovered how mutations related to a group of movement disorders produce their effects. Published in Proceedings of the National Academy of Sciences, the ...

Researchers explain how your muscles form

November 12, 2018
All vertebrates need muscles to function; they are the most abundant tissue in the human body and are integral to movement.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.