CAR-T Immunotherapies May Have a New Player


Source: University of California – San Diego

Summary: In a new study, researchers report that similarly modified natural killer (NK) cells derived from human induced pluripotent stem cells (iPSCs) also displayed heightened activity against a mouse model of ovarian cancer.


CAR-T cell-based immunotherapies have garnered considerable attention and investment in recent years. T-cells, a type of white blood cell, are extracted from a patient’s blood, genetically modified with a chimeric antigen receptor (the CAR) to bind with a certain protein on the patient’s cancer cells, grown in large numbers in a laboratory and then infused into the patient. Emerging CAR-T immunotherapies leverage modified versions of patient’s T-cells to target and kill cancer cells. In a new study, researchers at University of California San Diego School of Medicine and University of Minnesota report that similarly modified natural killer (NK) cells derived from human induced pluripotent stem cells (iPSCs) also displayed heightened activity against a mouse model of ovarian cancer. The study findings were published in the journal Cell Stem Cell.

Immune cells

Natural killer cells are immune cells that eliminate infected, foreign and cancer cells. Credit: NIAID

Early testing of CAR-T therapies have shown promise-and sometimes dramatic success-but there are distinct limitations. First, cells must be isolated from each individual-a process that takes significant time and money. Additionally, since T-cell therapy is designed to work only for that patient, some patients may not be able to have T cells collected, or they may not have time for this process before the tumor progresses. This means some patients who could potentially benefit will not be able to get CAR-T cell-based therapies. In their research, the researchers tested CAR NK cells derived from human iPSCs in an ovarian cancer xenograft mouse model, comparing their anti-tumor activity against other versions of NK cells and CAR-T cells. The former demonstrated similar activity to CAR-T cells, but with less toxicity.

Prof. Dan Kaufman said, “data indicated ovarian cancer was a good first target, but that other solid tumors, such as breast cancer, brain tumors, and colon cancers, as well as blood cell cancers such as leukemias are also likely to be suitable targets of iPSC-derived NK cells”.


More Information: Ye Li et al, “Human iPSC-Derived Natural Killer Cells Engineered with Chimeric Antigen Receptors Enhance Anti-tumor Activity”, Cell Stem Cell (2018). DOI: 10.1016/j.stem.2018.06.002 


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