A domestic research team has identified a new mechanism that suppresses the anti-tumor function of NK (natural killer) cells, which are immune cells that attack cancer cells.
On the 12th, it was announced that a joint research team led by Professor Yoon Mi-sun of the Department of Radiation Oncology at Hwasun Chonnam National University Hospital and Professor Jo Deok of Samsung Seoul Hospital identified a new "intracellular immune checkpoint" that suppresses the anti-tumor function of NK cells, and proposed a strategy to enhance the cancer cell attack power and sustained anti-tumor function of NK cells by removing it.
NK cells are representative innate immune cells that find and eliminate cancer cells. CAR-NK is an immunotherapy agent in which chimeric antigen receptors (CARs) that recognize cancer cells are introduced into NK cells to enhance their anti-tumor function. While it is attracting attention as a next-generation therapy because it can be created using another person's cells, it has the limitation that NK cell function declines and it is difficult to sustain anti-tumor effects when exposed for long periods to inflammation and immunosuppressive environments around tumors.
The research team focused on "PTPN22," a protein that regulates immune function inside NK cells, and used CRISPR/Cas9 gene editing technology to create NK cells with PTPN22 removed, evaluating their anti-tumor function. As a result, NK cells with PTPN22 removed showed enhanced ability to attack cancer cells and maintained their anti-tumor function for longer even in unfavorable environments around tumors.
In particular, CAR-NK targeting the CD19 protein on the surface of B cells, which are immune cells affected by cancer, showed improved killing ability (cancer cell destruction capacity) against hematological cancer cells. Anti-tumor function was also enhanced in CAR-NK targeting mesothelin (MSLN), confirming the possibility of application to various CAR-NK therapies.
The research team reported that animal experiments also showed that CD19 CAR-NK92 cells with PTPN22 removed effectively suppressed leukemia growth and significantly extended survival periods compared to ordinary CAR-NK92 cells.
The research team stated that they have completed patent registration for two technologies related to this study and filed additional patents. Yoon Mi-seon (Prof.) said, "We were the first to identify that PTPN22 plays a role as an important intracellular immune checkpoint limiting the anti-tumor function of NK cells," adding, "Going forward, we will continue research to develop it into a new NK cell therapy platform targeting PTPN22 to enhance anti-tumor effects and treatment sustainability."
The study results were published in the international academic journal "Journal for ImmunoTherapy of Cancer" in the field of immunotherapy.
in THEBIO
