Incorporation of bacterial immunoevasins to protect cell therapies from host antibody-mediated immune rejection.

ABSTRACT: Cellular therapies are engineered using foreign and synthetic protein sequences, such as chimeric antigen receptors (CARs). The frequently observed humoral responses to CAR T cells result in rapid clearance, especially after re-infusions. There is an unmet need to protect engineered cells from host-versus-graft rejection, particularly for the advancement of allogeneic cell therapies. Here, utilizing the immunoglobulin G (IgG) protease "IdeS," we programmed CAR T cells to defeat humoral immune attacks. IdeS cleavage of host IgG averted Fc-dependent phagocytosis and lysis, and the residual F(ab')₂ fragments remained on the surface, providing cells with an inert shield from additional IgG deposition. "Shield" CAR T cells efficiently cleaved cytotoxic IgG, including anti-CAR antibod

SUBMITTER: Peraro L 

PROVIDER: S-EPMC8636170 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature