CRISPR-Cas9编辑,CAR-T细胞疗法 z-bo 2020-09-30 400

　　According to the latest data released by researchers at the Abramson Cancer Center of the University of Pennsylvania, CAR-T cells that have undergone Crispr-Cas9 gene editing can persist in cancer patients for several months, and can stably proliferate and function.

　　This study is the first clinical trial to test human gene editing methods in the United States. In an article recently published in the journal Science, the researchers introduced their Phase I clinical trial of gene editing CAR-T treatment on three patients result.

　　"The data we obtained from the three patients proved two important things. First, we can accurately and successfully perform multiple edits during the manufacturing process; second, so far, these cells have shown continuous attack and killing. The ability to kill tumors," said Professor Carl June, the senior author of the article. This discovery is another achievement of the University of Pennsylvania as a pioneer in cell and gene therapy. The institution previously developed the first FDA-approved CAR-T cell therapy Kymriah for children and adults with blood cancer. The method in this study is closely related to CAR T cell therapy. In traditional CAR T cell therapy, the patient's immune cells are genetically modified to fight cancer. The method of this test is different. Like CAR T, the researchers in this study first collected T cells in the patient's blood. However, the researchers did not transfer any CAR receptor molecules targeting cancer cell antigens (such as CD19) to these T cells, but first used CRISPR/Cas9 editing to remove three key genes. Two of the genes express the natural receptors of T cells, namely TCRa and TCRb genes, and the third gene expresses PD-1, which is considered to be a key "checkpoint" molecule that regulates T cell activity.

　　"This new analysis of three patients has confirmed that the cells produced contain all three edits, thus confirming for the first time the ability of CRISPR/Cas9 technology to target multiple genes in humans at the same time."

　　Once these three genes are knocked out, lentivirus can be inserted into the cancer-specific synthetic T cell receptor to complete the fourth genetic modification. The modified T cell can target an antigen called NY-ESO-1 .

　　Compared with the original CAR-T cell's survival time in the body of less than one week, this new analysis shows that the edited cell can persist in the body for up to 9 months.

　　After a few months of infusion into the patient, the researchers drew more blood and isolated the CRISPR-edited cells for research. The results show that these cells still have the ability to kill tumors.

　　June said: "Previous studies have shown that these cells will lose their function within a few days. Therefore, the CRISPR-edited cells in this study can maintain their anti-tumor function for a longer period of time after a single infusion. The facts are encouraging."