CRISPR基因编辑,抵抗癌症 z-bo 2020-09-30 319

　　A few days ago, in the United States, researchers used gene editing tools to treat three patients with advanced cancer for the first time. At the same time, the results of the Phase 1 clinical trial showed high expectations. So far, this treatment is safe and will bring more consequences. It will be released soon. In order to develop safe and effective cancer treatments, scientists at the University of Pennsylvania and other institutions have developed advanced immunotherapy through research. During the treatment, the researchers removed the patient’s own immune cells from the body. In addition, these immune cells can be "trained" to recognize specific cancer cells, and finally these cells can be injected into the patient's body to effectively destroy the cancer cells that grow in the patient's body.

　　Unlike chemotherapy and radiation therapy (which can directly kill cancer cells), immunotherapy can activate and reactivate the patient's immune cells. Researchers use a gene editing tool called CRISPR to change immune cells to produce immune cells, cancer cells can be redirected and killed. Using this technology, researchers can develop highly effective immunotherapy with almost no side effects. The author is a pharmacist and biomolecular engineer. He is very interested in studying the development of new therapies. The author's laboratory focuses on editing with a gene editor. In particular, researchers have developed a CRISPR-based gene editor. You can better diagnose and treat cancer and other diseases. Researchers can combine chemistry, biology and nanotechnology to design, control, and provide gene editing tools more effectively and accurately.

　　train immune cells to detect and kill cancer

　　The first step in producing and killing tumor cells in cancer drug testing is T cells (pathogens and cancer cells) in the blood of cancer patients. Is to isolate a type of white blood cells that can resist) In this study, the researchers found two patients with advanced multiple myeloma and mucin/round cell liposarcoma (mucin/round cell liposarcoma). We recruited one patient to participate in the study. In order to arm T cells and enhance their anti-cancer ability without damaging normal cells, the researchers modified the T cells to lose three genes, adding one first, and then modifying the T. Inject cells. Let us return to cancer patients. Two missing genes can encode T cell receptors. It is a special protein on the surface of T cells that can recognize and bind antigen molecules of cancer cells. When these manipulated T cells bind to these antigens, they can directly attack and kill cancer cells, but the problem is that a single T cell can recognize various antigens in the body. It reduces the efficiency of finding and attacking cancer cells. By eliminating these two genes, T cells are less likely to attack the wrong target or host. This phenomenon is called autoimmunity.

　　In addition, the researchers also destroyed the programmed cell death protein 1 (Programmed Cell Death Protein 1), which is the third gene that can effectively slow down the human immune response. Destruction can increase the efficiency of T cells. The final step in transforming these cells is to add a gene that can produce a new type of T cell receptor that can recognize and capture a special marker called NY-ESO-1 on cancer cells. Eliminating three genes and adding one can make T cells effective against cancer.

　　Where is CRISPR in clinical trials?

　　So how do researchers edit T cells? They used CRISPR/Cas9 gene editing technology for research. It can play two roles. In other words, the targeted CRISPR molecule can find and bind to the target gene site, and Cas9 can cut the DNA and ultimately inactivate the gene. Using electroporation (temporary holes can be formed in the cell membrane) to transfer Cas9 protein and targeting molecules (targeting three genes) to millions of T cells.

　　After using CRISPR to block the function of these three genes, the researchers safely used the inactivated virus to transfer other genes to T cells (a cancer-specific marker NY-ESO). -1 can be recognized. In addition to the functions of these genes in millions of cells, it may take days or weeks to promote the growth of T cells into billions of cells in an in vitro culture dish. Four days before injecting CRISPR-modified T cells into patients, the Rewarm study provided each of the three patients with several chemicals to eliminate white blood cells present in the body. Finally, about 100 million/kg modified T cells are injected into the patient.

　　CRISPR's future potential

　　After T cell injection, the researchers monitored the patients continuously for the first 28 days, followed up for 6 months every month, and then checked the patients every 3 months. done. Observe the body's adverse reactions, such as immune reactions. This T cell therapy usually has a variety of side effects, including fever, muscle pain, headache, confusion, seizures, low blood pressure, bleeding disorders and multiple organs. At present, researchers have not found any signs of toxic effects in any patients. However, the first patient with advanced multiple myeloma continued to develop tumors after 60 days. The patient's treatment does not seem to be very successful, but the Phase 1 clinical trials conducted by the researchers are mainly treatment tests. Safety, researchers have not reported symptoms of poisoning. The researchers used tandem CT scans to monitor a second patient with advanced mucin-like circular cell liposarcoma. After 90 days of treatment, the patient's condition was relatively stable. The third patient with multiple myeloma has just started the trial with no results. The researchers said that this new treatment method based on CRISPR gene editing technology has no serious toxic effects in the treatment of cancer patients. This may be an important step for researchers to further advance clinical research work at a later stage.