Two-in-one CAR-NK therapy, effective against a variety of cancers!

  From the perspective of cancer treatment, some of the most promising advances are focused on immunotherapy, which can strengthen the patient's immune system to attack cancer. However, immunotherapy is not suitable for all patients, and researchers are always looking for ways to improve.

  Currently, researchers at Washington University School of Medicine in St. Louis are combining two immunotherapies into one therapy, which is the study of human cells and mice, which can be used to treat certain blood cancers (such as leukemia). The combination of the two treatments is more effective than the single treatment. The research was published in the online version of the Journal of Blood. Evidence also suggests that this new method may be safer than the recent FDA-approved cellular immunotherapy called CAR-T cell therapy.

  CAR-T cell therapy is to transform T cells in the immune system into target tumor cells. Cellular immunotherapy is most commonly used to treat blood cancers, but it can also be used to treat certain solid tumors, such as prostate cancer, lung cancer, and melanoma. In this new study, the scientists used a technique to modify CAR-T cells, instead of modifying special immune cells called T cells, but using a similar technique to create natural killer cells (NK). Various immune cells. The resulting immunotherapy may combine the advantages of these two strategies to reduce the accidental side effects of CAR-T cell therapy. For example, in some patients, CAR-T cell therapy can cause a cytokine storm, which is a life-threatening immune system overreaction. Immunotherapy has broad prospects in cancer treatment, but researchers need to provide more effective and safer methods for more patients. This combination therapy is based on a natural killer cell-based treatment strategy developed by researchers for leukemia patients. They can pressurize natural killer cells and enhance their ability to attack cancer cells. At the same time, researchers can use the genetic engineering technology of CAR cell therapy to direct natural killer cells to tumor targets that are usually ignored by NK cells. It fundamentally changes the types of cancer that NK cells can be used to treat, including other hematological cancers and potential solid tumors.

  According to previous studies, researchers can collect the patient’s own NK cells and expose them to specific chemical signals to attack the tumor and send them back to the prepared cells. .. The patient receives treatment. Researchers say that exposure to chemicals is basic training for cells to make NK cells fight cancer. When these cells return to the body, they will remember the training they received. In other words, it can attack tumor cells more effectively. Researchers call them memory NK cells because the training allows them to remember what to do when they encounter tumor cells.

  In a small clinical trial conducted at the Sitman Cancer Center of Burns Jewish Hospital and Washington University School of Medicine, these cells can effectively provide sustained relief for certain leukemia patients, but it is not suitable for humans. Even if some tumor cells undergo basic training, they still avoid memory of NK cells. In order to help cells find tumor cells, perform basic training and kill suitable targets, researchers have discovered CAR (Chimeric Antigen Acceptance) that is usually used to find T cells as tumor cells. The memory NK of molecules in the body changes. cell. CAR molecules are extremely flexible and can be modified according to the proteins on the surface of cancer cells to guide cells to different types of tumors. This kind of mixed cells is more effective than simply using memory NK cells to treat leukemia mice, and can extend the survival time of mice treated with CAR memory NK cells. The researchers also found that despite the relatively low dose of cells given to the mice, the treatment was still effective.

  The most exciting part of this study is that these heterozygous NK cells proliferate well in mice and respond to tumors. We provide very small doses and you can see incredible tumor control. For researchers, this highlights the potential of these cells and their potential for expansion in vivo. This is very important for translating these findings into the clinic.

  Researchers said: All clinical trials that study all types of NK cells have not shown the annoying side effects of CAR-T cells, which may severely affect patients' cytokine release syndrome or neurotoxicity. These side effects may be dangerous, and life requires special attention. We are still studying the differences between NK cells, but the benefits of CAR-T cells have almost no side effects. If possible, this is a reasonable research direction. Another benefit of this safer treatment is that these cells can be injected into the patient's body early in the disease, rather than as a last resort. Other research groups have also developed CAR-NK cells, but the main difference is that the NK cells of other research groups are cord blood or induced cells, rather than adult donors or patients themselves. It is derived from stem cells.

  Feinig, the corresponding author of the study, said: "Other research groups have artificially differentiated stem cells into cells similar to NK cells. This method cannot guarantee that these cells have all the characteristics of typical mature NK cells. Beginning with adult NK cells, we are confident that they have all the characteristics and behaviors unique to adult NK cells, and are effective for certain types of cancer patients (especially leukemia patients). Durability and effectiveness for a variety of cancers: next In the next few years, the process will be extended to include enough cells for the first human clinical trials. I want to generate and study their effectiveness against different types of human hematological cancers.