CRISPR technology is used for cancer patients in the United States for the first time!

Recently, the top academic journal Science published the latest progress of a clinical trial of cancer immunotherapy online Three patients with refractory cancer received a new T cell therapy combined with gene editing technology It is of concern that this is the first time in the United States to test cell therapy based on CRISPR gene editing in cancer patients This new type of T-cell therapy is similar to the car-t cell we often hear, which is to fight cancer by transforming the patient's own immune system Researchers need to collect T cells from patients' blood, insert therapeutic T cell receptor (TCR) through gene engineering in vitro, and recognize the typical protein NY-ESO-1 of cancer cells This cancer antigen provides a target with high specificity and weak side effects for T cell therapy Compared with car-t cell therapy, tcr-t cell therapy has less life-threatening adverse events such as cytokine release syndrome On the basis of T cell therapy, crispr-cas9 gene editing technology provides a powerful tool for enhancing the natural anti-cancer ability of T cells Before TCR was inserted, the researchers used CRISPR to knock out three genes in T cells Two of them are TCR genes of T cells, which can avoid the mismatch or competition between natural TCR and gene engineering inserted receptors, and improve the therapeutic TCR effect The third gene is the gene encoding PD-1 receptor Just as immune checkpoint inhibitors that inhibit the function of PD-1 protein can help T cells remove the "brake", gene editing knockout of PD-1 receptor can also enhance T cell activity and avoid T cell depletion ▲ schematic diagram of this new T cell therapy (picture source: reference [1]) In order to test the practical feasibility and safety of this concept, the researchers conducted a phase 1 clinical trial "This trial focuses on three questions: can we edit T cells in this particular way? Is the T cell still functional? Can these cells be safely returned to the patient? " Dr Edward stadtmauer, lead author of the study and chair of clinical trials, said "Early data show that the answer to all three questions is yes." In the published results, the T cells edited by these genes did not lead to serious treatment-related adverse reactions, and showed long-term survival and expansion ability Of the three cancer patients in the study, two were refractory advanced myeloma and one was refractory metastatic sarcoma All the standard therapies they received in the past were ineffective After receiving T cell reinfusion, the engineered T cells can still be detected in the patient's body after gene editing for up to 9 months And when researchers isolated genetically edited T cells from patients and took them back to the lab for testing, they found that they still had the ability to kill cancer cells ▲ crispr-cas9 engineered T cells continued to expand and survive in 3 patients (picture source: reference [1]) "Previous studies have shown that these cells will lose their function in a few days, but now the results show that the cells edited by CRISPR can maintain their anti-cancer function for a long time after a single injection, which is very encouraging!" Professor June said The researchers also mentioned that the preliminary clinical results have acceptable safety, but it will take more patients and longer observation to fully evaluate the safety of this new method before it can really enter the clinical treatment In addition, whether the engineered T cells after gene editing are effective for advanced cancer is also an important question for follow-up research The researchers said the new data will open the door for later research to continue to investigate whether the new method can be extended to a wider range of cancer treatment It is expected that gene editing technology will benefit more cancer patients in the near future reference material: [1] Edward A Stadtmauer et al., (2020) CRISPR-engineered T cells in patients with refractory cancer Science DOI: Doi: 10.1126 / science.aba7365 [2] First phase i clinical trial of CRISPR-edited cells for cancer shows cells safe and durable Retrieved Feb 10, 2020, from https://