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CRISPR-engineered T cells in patients with refractory cancer

2020-03-16 20:48

Tumor immunotherapy brings new strategies and hope to tumor treatment. The use of immune cells for anti-tumor treatment has greatly improved the clinical treatment of tumors. Recently, Carl H. June and Edward A. Stadtmauer's team from the University of Pennsylvania's Perelman School of Medicine published an article in Science that reported the first clinical study using CRISPR-Cas9 to edit multiple genes in T cells for immunotherapy. 

The research team used CRISPR-Cas9 to knock out TRAC and TRBC genes encoding endogenous TCR chains in T cells to increase the expression of tumor-specific TCR genes transduced by lentivirus, simultaneously using CRISPR-Cas9 to knock out the PDCD1 gene encoding PD-1 also reduces the depletion of returning T cells. Initially, there were six participating patients, but only four patients obtained gene-edited T cells in vitro. One patient deteriorated and died before returning, and in the end, only three patients returned CRISPR-Cas9-edited T cells. 

In summary, this Phase I clinical trial is the first to demonstrate the feasibility and safety of using CRISPR-Cas9 to edit multiple genes in T cells for immunotherapy in patients (first-in-human). Subsequently, trials require more patients to participate, return T cells with higher gene editing efficiency, and observe for a longer period of time to further evaluate the safety of the strategy and its therapeutic effect. 


Reference:

https://science.sciencemag.org/content/early/2020/02/05/science.aba7365/tab-pdf