CAR-NK therapy is a new type of immunotherapy in the treatment of cancer treatment. Immunotherapy has revolutionized the way cancer is treated. Cancer immunotherapy is divided into two categories: one is immune checkpoint inhibitors, and PD-1, PD-L1 and CTLA-4 have been approved for the treatment of a variety of cancers. And the 2018 Nobel Prize in Physiology or Medicine awarded the contribution of the development of immune checkpoint inhibitors to humans.
The other is cellular immunotherapy, in which the chimeric antigen receptor CAR-T therapy is the most rapidly progressing one. In 2017, the US Food and Drug Administration (FDA) approved two CAR-T cell therapies, Yescarta and Kymriah, which mainly target hematological tumors, leukemias and lymphomas.
CAR-T therapy has a long way to go to treat solid tumors, so scientists have begun to seek other cellular immunotherapies to treat cancer, and natural killer (NK) cell therapy is one of the most promising methods. The success of CAR-T cell therapy has stimulated enthusiasm for modifying NK cells with CAR genes to enhance their tumor-killing ability.
Recently, the results of a phase I / IIa trial of the MD Anderson Cancer Center in the United States announced that CD19-targeted umbilical cord blood chimeric antigen receptor natural killer cell therapy (CAR-NK) has achieved a clinical response. No major toxicities were observed in patients with refractory or refractory non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL).
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CAR-NK cell research data
The results of the trial were published yesterday in the New England Journal of Medicine. Of the 11 patients participating in the study, 8 (73%) responded to the treatment, and 7 of them responded completely, meaning that they no longer showed signs of cancer at a median follow-up of 13.8 months, and no patients experienced cells Factor release syndrome or neurotoxicity.
The response to CD19 CAR-NK cell therapy was significant within 1 month after the infusion, and the persistence of these cells was still detected within 1 year after the infusion.
Corresponding author Katy Rezvani, Professor of Stem Cell Transplantation and Cell Therapy, said: “We are encouraged by the results of the clinical trial, which will carry out further clinical studies to study the potential of allogeneic cord blood-derived CAR-NK cells as a patient in need Treatment options. “
At MD Anderson Cancer Center, NK cells were isolated from donated umbilical cord blood and genetically engineered to express the required CAR, which can identify cancer-specific targets. CAR-NK cells also need to be “equipped” with IL-15, an immune signaling molecule designed to enhance cell proliferation and survival.
In this study, CAR-NK cells are allogeneic, which means that these cells are taken from healthy donors that are not related to the patient, not the patient itself. Therefore, CAR-NK cells have the potential to be manufactured and stored in advance for immediate use. In contrast, currently commercially available CAR-T cells need to use a multi-week culture proliferation process to produce T cells that are genetically engineered based on the patient’s own genes.
CAR-NK cells have multiple advantages over CAR-T cells
First, unlike CAR-T cells, CAR-NK cells retain the inherent ability to recognize and target tumor cells through their natural receptors, so that when CAR-NK targeted therapy is used, tumor cells are less likely to escape killing.
Second, CAR-NK cells do not undergo immune rejection for days to weeks. As a result, they have not shown the same safety issues in many CAR-T clinical trials, such as the absence of cytokine release syndrome.
Finally, NK cells do not require strict HLA matching and do not have the potential to cause graft-versus-host disease, which is an important risk for CAR-T cell immunotherapy.
