NEJM: True universal no matching! Clinical studies showed that CAR-NK treatment had a total remission rate of 73%, and a donor cord blood could produce 100 copies of CAR-NK

In recent years, CAR-T therapy has been like entering deep waterThe odd dot saw either long-term efficacy data or the entry of a new pharmaceutical giant, a stunning new achievement that seems to have been around for some timeno way, existing CAR-T therapy does have some obstacles, such as the need to use the patient's own T cells, the individual preparation process is quite difficult, and T-cells too strong immune response, may also lead to serious side effectsCAR-T doesn't have a hard time trying to get away(Picture: Nature Reviews Clinical Oncology)but there's an old saying that it's more difficult than thatThe use of CAR to transform immune cells and enhance their combat effectiveness is still promisingCAR-T is uncertain, maybe CAR-NK, CAR-macrophage can do it?recent lying in the New England Journal of Medicine, a new clinical trial showed that CAR-NK cells targeting CD19 had a 73% (8/11) remission rate for cancer in the blood system, 7 of which were completely remissionable!single mitigation rate data, CAR-NK has been able to fight with CAR-T therapy, and the treatment is not only safe, quick lying, the effect is also very long-lasting, breaking through the previous NK cell therapy persistence is not strong bottleneckeven more amazing is the preparation of this CAR-NK therapy, using NK cells from other donors' umbilical cord blood and not requiring an HLA type to be used! The results, from the MD Anderson Cancer Center, are arguably the first shot at cell therapy in 2020It is said that some people think that the generic CAR-T will be CAR-NK to do ..(Picture source: Science)to the ability to kill cancer cells, NK cells are actually better than T cells, and NK cells are more widely sourced, can come from peripheral blood, cord blood and pluripotent stem cells, the source and quantity is not a problem, and NK cell killing does not need to be like T-cells, experience antigen sygeny this step, do not need HLA configurationbut everything has its advantages and disadvantagesNK cells in the human body accounted for a low proportion, short life, weak continuous amplification capacity, the same restrictions on their use, under normal circumstances can only be anti-tumor immunity of the side so to really make the use of CAR-NK cells a reality, we have to solve these problems, instead of just inserting antigen receptor technology to target CD19 non-Hodgkin's lymphoma (NHL) and chronic lymphoblastic leukemia (CLL) in this clinical trial, the mD Anderson Cancer Center team edited the leukyle-15 (IL-15) gene in NK cells during the second editing phase, after studies showed that it allowed NK cells to survive at least every doubling In fact, the road map for NK cell immunotherapy has long been drawn (Picture: Nature Reviews Drug Discovery) in addition to survival time, the safety of cell therapy is also the focus, although in theory, CAR-NK cells trigger cytokine release syndrome and other serious adverse events, the risk is lower than CAR-T cells, but the research team added "suicide switch" Caspase 9 edited, and the next step is preparation Because it was an early clinical trial, the research team started with caution and increasing doses in NK cell dosage and donor matching, and the HLA matching of the first nine patients was partially compatible with the treated patient, until the final treatment of the two patients, the matching criteria were released and for safety, each patient in the group is treated at least two weeks apart from the previous one, so each patient receives CAR-NK treatment, which is prepared separately But technically, the team has long been able to prepare more than 100 copies of CAR-NK therapy, relying on a donor's umbilical cord blood after all, patients have undergone many rounds of treatment, a little more cautious, and again, clinical trials, the final look is the efficacy and safety Of the 11 patients in the trial group, 8 achieved remission within 30 days of injection of CAR-NK cells, 7 of whom were completely remissionable, with a real effect Of course, there is a patient who is not good at treatment however, it is worth noting that five of the eight patients received other treatments after the remission, such as inamine, Venetoclax and bone marrow transplants, so the PFS, duration of the remission (DoR) and other indicators in this trial were not included the research team is more concerned about THE amplification capacity and survival time of CAR-NK cells injected into the patient' body, in both cases, CAR-NK cells are not poor performance, the number of injections 3 days later began to expand, survival time in some patients can be more than 1 year! The long-term presence of CAR-NK cells also led to only a number of hematology adverse events of 3-4, but these had no significant effect on the treatment as a whole, so much so that the team did not activate the "suicide switch" good, safer, easy to prepare and not selected, these benefits add together, so that the research team is very satisfied with the results The MD Anderson Cancer Center has partnered with Takeda Pharmaceuticals and is expected to launch a clinical Phase II trial of CAR-NK therapy in 2021