CXCL10-induced chemotaxis of <i>ex vivo</i>-expanded natural killer cells combined with NKTR-255 enhances anti-tumor efficacy in osteosarcoma.

ABSTRACT: Osteosarcoma (OSA) has a dismal prognosis despite surgical resection and multiagent chemotherapy. While adoptive natural killer (NK) cell therapies have been successful in hematological malignancies, the application in solid tumors is challenging due to a tumor microenvironment (TME) that impairs NK cell tumor infiltration. Here, we found that ex vivo expansion of NK cells significantly increases the expression of C-X-C motif chemokine receptor 3 (CXCR3), one of the major proteins in the regulation of NK cell chemotaxis. Engineered over-secretion of CXCR3 ligands, C-X-C motif chemokine ligand (CXCL)9, -10, or -11, from OSA cells significantly enhanced expanded NK cell migration toward OSA cells in vitro and infiltration into the TME in vivo, with the highest NK infiltr

SUBMITTER: Eguchi S 

PROVIDER: S-EPMC12509742 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature