Science Spotlight: Preventing NK cells from rejecting allogeneic therapies, and more

Karolinska Institute researchers devised a new method to reduce rejection of allogeneic CAR T and CAR NK cells without affecting their antitumor function. The method centers on deleting a pair of ligands involved in adhesion of host cells to donor cells.

Silencing of B2M and CIITA, which reduce cell surface expression of HLA class I and class II, respectively, were previously shown to help evade T cell-mediated rejection of CAR cell therapies, but the absence of the receptors prevents host NK cells from recognizing the grafted cells as “self,” which can also lead to rejection. The Cell Stem Cell article authors showed that deletion of two additional surface proteins from the therapeutic cells — adhesion ligands ICAM-1 and CD58 — limited NK cell activation, facilitating immune escape...