Chimeric antigen receptors (CARs) significantly enhance the anti-tumor activity of immune effector cells. Current CAR-based immunotherapies leverage engineered versions of a patient’s own T-cells to target and kill cancer cells. Recently, a study led by researchers at University of California San Diego School of Medicine and University of Minnesota demonstrated that similarly modified CAR constructs can also improve natural killer (NK) cell-mediated killing
NK cell-based immunotherapies may offer distinct advantages over T cells. Unlike T cells, NK cells do not require human leukocyte antigen (HLA) matching in order to mediate their activity. Thus, NK cells may function as allogeneic effectors, without the need for time-consuming collection and modification of patient-sourced cells. As a result, NK cells may be able to serve as an off-the-shelf immunotherapy without patient matching.
In the study, researchers identified a CAR containing the transmembrane domain of NKG2D, the 2B4 co-stimulatory domain, and the CD3ζ signaling domain to mediate strong antigen-specific NK cell signaling. Expression of these CAR constructs in NK cells derived from iPSCs significantly improved NK cell mediated cytotoxicity against antigen-expressing leukemia targets and ovarian cancer targets. Furthermore, when these CAR NK cells were tested in an ovarian cancer xenograft mouse model, they were able to effectively inhibit tumor growth and prolong survival. It is impressive that the CAR NK cells demonstrated a potent ability to kill mesothelin-expressing tumors both in vitro and in vivo, while CAR T cells have historically struggled to provide only limited efficacy against solid tumors.
The article, titled “Human iPSC-Derived Natural Killer Cells Engineered with Chimeric Antigen Receptors Enhance Antitumor Activity” was published in Cell Stem Cell.