First gene-based therapy recommended for approval by the FDA

In a long-awaited milestone for genomic medicine, an expert panel convened by the US Food and Drug Administration has recommended, by unanimous vote, approval of the first chimeric antigen receptor (CAR) T-cell immunotherapy. The treatment, called CTL019, was approved for pediatric and young adult patients with B-cell acute lymphoblastic leukemia who have relapsed multiple times or become refractory to treatment. In these cases, the 5-year disease-free survival is 10-30%. In the trials cited in recommending the treatment, 83% (52/63) of patients achieved essentially complete remission within 3 months, with no minimal residual disease detected among responding patients. Many similar CAR T-cell therapies are on the verge of widespread clinical use to treat a variety of mainly blood-based cancers that have failed conventional treatment. Final approval is expected in October 2017. CTL019 developer Novartis plans additional regulatory filings for CTL019 in the United States and Europe to treat adults with diffuse large B-cell lymphoma. The personalized treatments, in which a patient's T cells are harvested and modified with an antigen known to be present on their type of cancer, prime the immune system to recognize and destroy cells containing the antigen. The concept has been coined a "living drug" because the modified T cells could potentially remain in a person's body in perpetuity, seeking out and destroying cancer cells long after the initial treatment. Widespread use of the CAR T-cell therapy would require a large investment in manufacturing sites capable of routinely carrying out the complex, exacting process of storing, transforming, and shipping harvested T cells. In addition, medical personnel at treatment centers will need to be trained to deal with the often life-threatening immune responses that can occur during CAR T-cell therapy. –Karyn Hede, News Editor

Scientists recreate “movie” using CRISPR gene editing

In a clever demonstration of CRISPR gene editing mastery, scientists have encoded a sequence of moving images in bacterial cells growing in culture. The recreation of a rider astride a galloping horse made famous in a series of vintage moving picture frames from the 1870s dramatically illustrates its potential. In recreating the iconic moving picture frame by frame, scientists simultaneously demonstrated the precise genetic control possible through the CRISP/Cas9 gene editing system and its potential to encode sequential information. The Harvard-based team envisions someday recording the changing internal states of cells using the system. It is also the first step in using DNA to encode not only genetic information but also any arbitrary sequential information. The CRISPR/Cas system, which evolved to provide a form of adaptive immunity in bacteria, includes a mechanism that, when harnessed, allowed the scientists to encode the binary values of “black” and “white” as a code delivered in series to the Escherichia coli bacteria growing in culture. To create the movie, the researchers sequenced the bacterial DNA and read the pixel nucleotide code, which was recapitulated at about 90% accuracy. The research team plans to use the principle established with bacteria to build the recording devices in other cell types and to confirm its ability to reliably encode sequential biological information. “One day, we may be able to follow all the developmental decisions that a differentiating neuron is taking from an early stem cell to a highly specialized type of cell in the brain, leading to a better understanding of how basic biological and developmental processes are choreographed,” said first author Seth Shipman, a postdoctoral scientist working in Harvard geneticist George Church's laboratory. –Karyn Hede, News Editor