Lipid anchor-mediated NK cell surface engineering for enhanced cancer immunotherapy

Abstract

Current natural killer (NK) cell-based cancer immunotherapy for the treatment of solid tumors often exhibits insufficient cancer recognition specificity, thereby limiting therapeutic anticancer efficacy, especially for triplenegative breast cancers (TNBCs). In this study, we develop artificial lipid-folate conjugates, for stable anchoring onto NK cell surfaces via hydrophobic interactions, thus augmenting folate-mediated ligand-receptor immune interactions with target cancers. This hydrophobized conjugate anchor provides additional cancer recognition ligands without any sophisticated genetic modification, and successfully enhances the anticancer efficacies of surface-coated NK (SCNK) cells without disturbing their intrinsic properties. Augmented cancer recognition ability sequentially promotes the secretion of cytolytic granules (granzyme and perforin) with cytokine (TNF-& alpha;), demonstrating improved cytotoxicity of the SCNK cells. Furthermore, the SCNK cells significantly infiltrate into the tumor site, inducing tumor apoptosis/necrosis, and suppressing tumor progression and metastasis in TNBC mouse models. Taken together, our artificial lipid-folate conjugates enable the treatment of solid tumors by augmenting the cancer-recognition and tumor targeting capacity of surface-engineered NK cells.