University of California San Francisco
Helen Diller Family Comprehensive Cancer Center

CRISPR-Based 'Discovery Engine' for New Cell Therapies to Advance Cancer Treatments

By Jeffrey Norris | | April 17, 2020

CRISPR-Based 'Discovery Engine' for New Cell Therapies to Advance Cancer Treatments

Despite centuries-long efforts to develop cures for cancer, various forms of the disease will kill about 630,000 people in the U.S. in 2020. But hopes are rising for cell therapies – sometimes called “living medicines” – that can boost and adapt the natural cancer-fighting potential of the immune system in ways that conventional cancer treatments cannot match.

UC San Francisco researchers now have reported a new method to design and test cell therapies, one they expect will speed the development of new life-saving treatments not only for cancer, but for other diseases, too.

Cell therapy for cancer is a type of immunotherapy. Immune-system cells known as T cells are isolated from a patient’s blood and genetically modified in the lab, inserting or removing genes so the cells will better recognize and destroy tumors. These modified T-cells are grown in culture until they number in the hundreds of millions, and are then infused back into the patient through an IV drip.

One form of cell therapy, known as CAR-T-cell therapy, is already approved for certain blood cancers, but so far cell therapies have not been effective against the “solid tumors” that affect the breast, colon, brain, lung, and other tissues.

In 2018, a UCSF team led by immunologist Alex Marson, MD, PhD, along with Theo Roth, an MD/PhD student in the UCSF Medical Scientist Training Program, developed a breakthrough technique in which they used pulses of electricity (a method called electroporation) to enable CRISPR gene-targeting technology to quickly and efficiently reprogram T-cells with new functions.

Now, in a study published April 16, 2020, in Cell, the team has advanced this technique to power a high-throughput platform to evaluate the specificity and potency of many different potential cell therapies simultaneously – comparable to the approach already widely used in industry to quickly screen large batches of small molecules to assess whether they would make effective drugs.