Glioblastoma is one of the most aggressive and common malignant brain cancer in adults. Approximately 20,000 people are diagnosed with glioblastoma annually in North America. Despite improvement of surgical technique and chemotherapy regimens, the 5 year survival rate remains low. Hence, the novel therapies for glioblastoma are urgently needed for better outcome of this dangerous disease.
Chimeric antigen receptor (CAR) modified T cells have gained tremendous clinical success in hematological malignancies. However, there’re some obstacles for extending the success of CARTs from liquid tumors to solid tumors.
Natural killer (NK) cells can be generated from peripheral blood, umbilical cord blood, human embryonic stem cells, induced pluripotent stem cells and even NK cell lines. NK cells respond to transformed and stressed cells, exerting cytotoxic effects to eradicate them. Therefore, NK cells are potential cell source for adoptive immunotherapy. Moreover, comparing to conventional CAR-T cells, CAR-NK cells have several advantages. (1) CAR-NK cells secrete less cytokines and maybe more safe than CAR-T cells; (2) NK cells are not responsible for graft-versus-host disease (GVHD) due to no HLA matching requirement. Therefore, CAR-NK cells have more potential to developing as off-the-shelf product for allogeneic infusion.
Recently, Toshiharu Murakami and colleagues transduced an anti-EGFRvIII CAR into a NK cell line KHYG-1, and the resulted CAR-NK cells exhibited potent killing efficacy towards glioblastoma cells in vitro. This finding demonstrated CAR-NK therapy may be an effective treatment option for glioblastoma patients.